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Novel device therapy shows continued benefits in pediatric peanut allergy
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.
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.
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.
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.
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.
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.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: A peanut protein–bearing skin patch shows favorable efficacy and safety as a treatment for peanut allergy, especially in children.
Major finding: After 1 year using the Viaskin Peanut device at the 250-mcg dose, one-third of formerly peanut-allergic children tolerated at least 1,000 mg of peanut protein in an oral food challenge; after 2 years using the patch, the rate increased to 60%.
Data source: Ongoing 2-year, open-label extension of the yearlong, double-blind, randomized VIPES trial of 171 peanut-allergic subjects aged 6-55 years.
Disclosures: The study was funded by DBV Technologies and presented by the company’s chief scientific officer.
ED visits due to anaphylaxis doubled at Canadian children’s hospital
The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.
“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.
As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.
The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.
The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.
The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.
“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.
As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.
The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.
The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.
The percentage of emergency department (ED) visits due to anaphylaxis more than doubled from 2011 to 2015 at one Canadian children’s hospital, according to a Research Letter to the Editor published in the Journal of Allergy and Clinical Immunology.
“Our results are limited to one pediatric center, but they suggest a worrisome increase in anaphylaxis rate that is consistent with the worldwide reported increase,” said Dr. Elana Hochstadter of the Hospital for Sick Children, University of Toronto, and her associates. The investigators analyzed longitudinal data in a national registry of anaphylaxis cases to track time trends for the disorder at their hospital. They identified 965 cases presenting to their ED during a 4-year period. The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41%. The overall volume of ED visits and the volume of specific ED diagnoses did not change during this interval.
As in other studies of anaphylaxis around the world, food was the most common trigger in this series, responsible for 82% of cases. Peanut was the most common food allergen, accounting for 22% of cases. Most reactions were of moderate severity, and the percentages of mild, moderate, and severe reactions remained relatively stable throughout the study period. The presence of asthma was associated with increased severity of anaphylaxis (odds ratio, 2.3), as was the presence of eczema (OR, 2.1). Only half of the patients who had an epinephrine autoinjector used it before presenting to the ED, Dr. Hochstadter and her associates said (J Allergy Clin Immunol. 2016 doi: 10.1016/j.jaci.2016.02.016). The median age of the patients was 6 years.
The reason for this rapid increase is unknown, but it parallels that reported in studies of anaphylaxis throughout North America and Europe. “An important observation in our study is that administration of epinephrine before arrival in the ED is independently associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, suggesting that prompt epinephrine administration is beneficial,” they noted.
The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.
FROM JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Key clinical point: The percentage of ED visits due to anaphylaxis more than doubled at one Canadian children’s hospital between 2011 and 2015.
Major finding: The percentage of all ED visits accounted for by anaphylaxis rose from 0.20% to 0.41% during the 4-year study.
Data source: A single-center longitudinal analysis of 965 ED visits for anaphylaxis.
Disclosures: The Allergy, Genes, and Environment Network Centres of Excellence, Health Canada, and Sanofi funded the study. Dr. Hochstadter and her associates reported having no relevant disclosures.
Paperwork snarls stand between kids and at-school asthma medications
BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.
The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.
Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.
In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.
The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.
“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.
In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.
Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.
Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”
In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”
The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).
On Twitter @karioakes
*In a previous version, Dr. Antos' name was misspelled.
Dr. Susan Millard, FCCP: comments: The issues identified in this article are huge and not just an occurrence in the inner cities. The critical problem is that the children are even more at risk when living in the inner cities and for sudden death due to asthma. Having one form for the whole state would help tremendously because we could print out an asthma action plan and the form for the school and then fax it directly!
Dr. Susan Millard, FCCP: comments: The issues identified in this article are huge and not just an occurrence in the inner cities. The critical problem is that the children are even more at risk when living in the inner cities and for sudden death due to asthma. Having one form for the whole state would help tremendously because we could print out an asthma action plan and the form for the school and then fax it directly!
Dr. Susan Millard, FCCP: comments: The issues identified in this article are huge and not just an occurrence in the inner cities. The critical problem is that the children are even more at risk when living in the inner cities and for sudden death due to asthma. Having one form for the whole state would help tremendously because we could print out an asthma action plan and the form for the school and then fax it directly!
BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.
The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.
Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.
In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.
The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.
“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.
In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.
Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.
Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”
In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”
The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).
On Twitter @karioakes
*In a previous version, Dr. Antos' name was misspelled.
BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.
The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.
Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.
In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.
The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.
“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.
In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.
Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.
Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”
In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”
The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).
On Twitter @karioakes
*In a previous version, Dr. Antos' name was misspelled.
AT THE PAS ANNUAL MEETING
Key clinical point: Four out of five high-risk elementary school children lacked proper orders for at-school asthma medication administration.
Major finding: The average number of elementary school children with asthma medication orders on file was 21% at year’s end.
Data source: Yearlong study of 10 inner-city Milwaukee elementary schools; enrollees with asthma ranged from about 40 to nearly 200.
Disclosures: The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).
Food Allergy Development Linked to S aureus Colonization in Children With AD
Staphylococcus aureus colonization is associated with development of food allergy in children with atopic dermatitis (AD), according to a letter to the editor from Dr. Andrea L. Jones and her associates.
In a study of 718 patients with AD, median food allergen–specific IgE levels to peanut were highest in patients with methicillin-resistant Staphylococcus aureus (MRSA) at 77.7 kilounits of allergen per liter. Patients with methicillin-sensitive S. aureus (MSSA) had median food allergen–specific IgE (sIgE) levels to peanut of 38.9 kUA/L, and patients without S. aureus had median sIgE levels to peanut of 4.3 kUA/L, below the 95% positive predictive value of oral food challenge reaction in patients of 14 kUA/L.
Total IgE levels were highest in AD patients with MRSA at 4,498 kU/L, but were also elevated in patients with MSSA at 2,709 kU/L, compared with 217 kU/L for patients without S. aureus colonization.
“Studies are needed to assess the association between S. aureus skin colonization and food allergy in patients with AD. Confirmation of our current observations opens up the possibility that therapy directed at eradicating S. aureus colonization will be important in the prevention of food allergen sensitization and possibly food allergy in patients with AD,” the investigators concluded.
Find the full letter in the Journal of Allergy and Clinical Immunology (2016 Apr. doi: 10.1016/j.jaci.2016.01.010).
Staphylococcus aureus colonization is associated with development of food allergy in children with atopic dermatitis (AD), according to a letter to the editor from Dr. Andrea L. Jones and her associates.
In a study of 718 patients with AD, median food allergen–specific IgE levels to peanut were highest in patients with methicillin-resistant Staphylococcus aureus (MRSA) at 77.7 kilounits of allergen per liter. Patients with methicillin-sensitive S. aureus (MSSA) had median food allergen–specific IgE (sIgE) levels to peanut of 38.9 kUA/L, and patients without S. aureus had median sIgE levels to peanut of 4.3 kUA/L, below the 95% positive predictive value of oral food challenge reaction in patients of 14 kUA/L.
Total IgE levels were highest in AD patients with MRSA at 4,498 kU/L, but were also elevated in patients with MSSA at 2,709 kU/L, compared with 217 kU/L for patients without S. aureus colonization.
“Studies are needed to assess the association between S. aureus skin colonization and food allergy in patients with AD. Confirmation of our current observations opens up the possibility that therapy directed at eradicating S. aureus colonization will be important in the prevention of food allergen sensitization and possibly food allergy in patients with AD,” the investigators concluded.
Find the full letter in the Journal of Allergy and Clinical Immunology (2016 Apr. doi: 10.1016/j.jaci.2016.01.010).
Staphylococcus aureus colonization is associated with development of food allergy in children with atopic dermatitis (AD), according to a letter to the editor from Dr. Andrea L. Jones and her associates.
In a study of 718 patients with AD, median food allergen–specific IgE levels to peanut were highest in patients with methicillin-resistant Staphylococcus aureus (MRSA) at 77.7 kilounits of allergen per liter. Patients with methicillin-sensitive S. aureus (MSSA) had median food allergen–specific IgE (sIgE) levels to peanut of 38.9 kUA/L, and patients without S. aureus had median sIgE levels to peanut of 4.3 kUA/L, below the 95% positive predictive value of oral food challenge reaction in patients of 14 kUA/L.
Total IgE levels were highest in AD patients with MRSA at 4,498 kU/L, but were also elevated in patients with MSSA at 2,709 kU/L, compared with 217 kU/L for patients without S. aureus colonization.
“Studies are needed to assess the association between S. aureus skin colonization and food allergy in patients with AD. Confirmation of our current observations opens up the possibility that therapy directed at eradicating S. aureus colonization will be important in the prevention of food allergen sensitization and possibly food allergy in patients with AD,” the investigators concluded.
Find the full letter in the Journal of Allergy and Clinical Immunology (2016 Apr. doi: 10.1016/j.jaci.2016.01.010).
FROM THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Study Reaffirms That Maternal Flu Immunization Reduces Infants’ Risk for Flu
Infants born to mothers who received flu immunization during pregnancy were 70% less likely to contract lab-confirmed influenza and 81% less likely to be hospitalized for flu before age 6 months, compared with infants of unimmunized mothers, a study reaffirmed.
Yet just one in ten pregnant women received the vaccine, a proportion that has steadily risen since the 2009-2010 H1N1 flu season.
“The results of this large retrospective study support the conclusions of prospective studies regarding the protective benefit of maternal influenza immunization during pregnancy,” reported Dr. Julie H. Shakib of the University of Utah, Salt Lake City, and her associates (Pediatrics. 2016 May 3. doi: 10.1542/peds.2015-2360). “Interventions that target both healthy pregnant women and those with chronic conditions are needed to increase vaccine uptake,” they wrote.
The researchers analyzed self-reported seasonal influenza immunization uptake in the 245,386 women who gave birth between December 2005 and March 2014 in the Intermountain Healthcare facilities in Utah and Idaho. Although 10% of the women overall received flu vaccinations, just 2.2% of the women who delivered before the 2009-2010 H1N1 pandemic had received them. That number rose after the pandemic to 21% (P < .001). More than half (52%) of the women giving birth during the 2013-2014 flu season reported getting the seasonal flu vaccine.
Among the women’s 249,387 infants, 866 had at least one influenza-like illness (ILI), including 32 born to vaccinated women and 834 born to unvaccinated women. The infants born to women receiving the flu vaccine during pregnancy were 64% less likely to develop an ILI, with illnesses in 1.34 per 1,000 born to vaccinated women and 3.7 per 1,000 born to unvaccinated women (relative risk, 0.36).
The rates of laboratory-confirmed influenza in the 658 children who contracted it were 0.84 per 1,000 children born to vaccinated mothers and 2.83 per 1,000 children born to unvaccinated mothers, translating to a 70% lower risk of flu in those born to vaccinated mothers (RR, 0.30). Similarly, infants born to vaccinated mothers were 81% less likely to be hospitalized for lab-confirmed influenza (RR, 0.19, P = .005). Just 3 of 151 hospitalized infants had been born to mothers who received the flu vaccine, for a rate of 0.13 per 1,000 for children of vaccinated mothers and 0.66 per 1,000 for children of unvaccinated mothers.
Pregnant women with public insurance or no insurance were less likely to report getting the seasonal vaccine than were privately insured women, but those with chronic conditions were more likely to be vaccinated. Uptake also was lower among women with incomes below the federal poverty level and among women living in either rural or frontier areas or in the Urban South or Southwest Intermountain regions.
“The Intermountain Urban South region includes Utah County, 1 of 30 U.S. counties with the largest estimated numbers of unvaccinated children from 1995-2001 CDC National Immunization Surveys (NIS) data,” the authors wrote. “It is possible that factors leading to parental vaccine hesitancy in children may similarly affect pregnant women considering maternal immunization during pregnancy.”
Because of widespread testing for respiratory viruses at Intermountain facilities, the researchers also could determine that flu vaccine receipt among the mothers did not affect incidence of RSV.
“Our study strengthens the evidence that maternal immunization provides passive protection against influenza to infants during the vulnerable period before they are old enough to receive active immunization,” Dr. Shakib and her associates wrote.
The research was funded by the National Institutes of Health, the University of Utah Children’s Health Research Center and the Pediatric Clinical and Translational Scholar Program, the H.A. and Edna Benning Presidential Endowment, and the University of Utah Center for Clinical and Translational Science through the National Center for Research Resources and the National Center for Advancing Translational Sciences. The authors reported no disclosures.
Infants born to mothers who received flu immunization during pregnancy were 70% less likely to contract lab-confirmed influenza and 81% less likely to be hospitalized for flu before age 6 months, compared with infants of unimmunized mothers, a study reaffirmed.
Yet just one in ten pregnant women received the vaccine, a proportion that has steadily risen since the 2009-2010 H1N1 flu season.
“The results of this large retrospective study support the conclusions of prospective studies regarding the protective benefit of maternal influenza immunization during pregnancy,” reported Dr. Julie H. Shakib of the University of Utah, Salt Lake City, and her associates (Pediatrics. 2016 May 3. doi: 10.1542/peds.2015-2360). “Interventions that target both healthy pregnant women and those with chronic conditions are needed to increase vaccine uptake,” they wrote.
The researchers analyzed self-reported seasonal influenza immunization uptake in the 245,386 women who gave birth between December 2005 and March 2014 in the Intermountain Healthcare facilities in Utah and Idaho. Although 10% of the women overall received flu vaccinations, just 2.2% of the women who delivered before the 2009-2010 H1N1 pandemic had received them. That number rose after the pandemic to 21% (P < .001). More than half (52%) of the women giving birth during the 2013-2014 flu season reported getting the seasonal flu vaccine.
Among the women’s 249,387 infants, 866 had at least one influenza-like illness (ILI), including 32 born to vaccinated women and 834 born to unvaccinated women. The infants born to women receiving the flu vaccine during pregnancy were 64% less likely to develop an ILI, with illnesses in 1.34 per 1,000 born to vaccinated women and 3.7 per 1,000 born to unvaccinated women (relative risk, 0.36).
The rates of laboratory-confirmed influenza in the 658 children who contracted it were 0.84 per 1,000 children born to vaccinated mothers and 2.83 per 1,000 children born to unvaccinated mothers, translating to a 70% lower risk of flu in those born to vaccinated mothers (RR, 0.30). Similarly, infants born to vaccinated mothers were 81% less likely to be hospitalized for lab-confirmed influenza (RR, 0.19, P = .005). Just 3 of 151 hospitalized infants had been born to mothers who received the flu vaccine, for a rate of 0.13 per 1,000 for children of vaccinated mothers and 0.66 per 1,000 for children of unvaccinated mothers.
Pregnant women with public insurance or no insurance were less likely to report getting the seasonal vaccine than were privately insured women, but those with chronic conditions were more likely to be vaccinated. Uptake also was lower among women with incomes below the federal poverty level and among women living in either rural or frontier areas or in the Urban South or Southwest Intermountain regions.
“The Intermountain Urban South region includes Utah County, 1 of 30 U.S. counties with the largest estimated numbers of unvaccinated children from 1995-2001 CDC National Immunization Surveys (NIS) data,” the authors wrote. “It is possible that factors leading to parental vaccine hesitancy in children may similarly affect pregnant women considering maternal immunization during pregnancy.”
Because of widespread testing for respiratory viruses at Intermountain facilities, the researchers also could determine that flu vaccine receipt among the mothers did not affect incidence of RSV.
“Our study strengthens the evidence that maternal immunization provides passive protection against influenza to infants during the vulnerable period before they are old enough to receive active immunization,” Dr. Shakib and her associates wrote.
The research was funded by the National Institutes of Health, the University of Utah Children’s Health Research Center and the Pediatric Clinical and Translational Scholar Program, the H.A. and Edna Benning Presidential Endowment, and the University of Utah Center for Clinical and Translational Science through the National Center for Research Resources and the National Center for Advancing Translational Sciences. The authors reported no disclosures.
Infants born to mothers who received flu immunization during pregnancy were 70% less likely to contract lab-confirmed influenza and 81% less likely to be hospitalized for flu before age 6 months, compared with infants of unimmunized mothers, a study reaffirmed.
Yet just one in ten pregnant women received the vaccine, a proportion that has steadily risen since the 2009-2010 H1N1 flu season.
“The results of this large retrospective study support the conclusions of prospective studies regarding the protective benefit of maternal influenza immunization during pregnancy,” reported Dr. Julie H. Shakib of the University of Utah, Salt Lake City, and her associates (Pediatrics. 2016 May 3. doi: 10.1542/peds.2015-2360). “Interventions that target both healthy pregnant women and those with chronic conditions are needed to increase vaccine uptake,” they wrote.
The researchers analyzed self-reported seasonal influenza immunization uptake in the 245,386 women who gave birth between December 2005 and March 2014 in the Intermountain Healthcare facilities in Utah and Idaho. Although 10% of the women overall received flu vaccinations, just 2.2% of the women who delivered before the 2009-2010 H1N1 pandemic had received them. That number rose after the pandemic to 21% (P < .001). More than half (52%) of the women giving birth during the 2013-2014 flu season reported getting the seasonal flu vaccine.
Among the women’s 249,387 infants, 866 had at least one influenza-like illness (ILI), including 32 born to vaccinated women and 834 born to unvaccinated women. The infants born to women receiving the flu vaccine during pregnancy were 64% less likely to develop an ILI, with illnesses in 1.34 per 1,000 born to vaccinated women and 3.7 per 1,000 born to unvaccinated women (relative risk, 0.36).
The rates of laboratory-confirmed influenza in the 658 children who contracted it were 0.84 per 1,000 children born to vaccinated mothers and 2.83 per 1,000 children born to unvaccinated mothers, translating to a 70% lower risk of flu in those born to vaccinated mothers (RR, 0.30). Similarly, infants born to vaccinated mothers were 81% less likely to be hospitalized for lab-confirmed influenza (RR, 0.19, P = .005). Just 3 of 151 hospitalized infants had been born to mothers who received the flu vaccine, for a rate of 0.13 per 1,000 for children of vaccinated mothers and 0.66 per 1,000 for children of unvaccinated mothers.
Pregnant women with public insurance or no insurance were less likely to report getting the seasonal vaccine than were privately insured women, but those with chronic conditions were more likely to be vaccinated. Uptake also was lower among women with incomes below the federal poverty level and among women living in either rural or frontier areas or in the Urban South or Southwest Intermountain regions.
“The Intermountain Urban South region includes Utah County, 1 of 30 U.S. counties with the largest estimated numbers of unvaccinated children from 1995-2001 CDC National Immunization Surveys (NIS) data,” the authors wrote. “It is possible that factors leading to parental vaccine hesitancy in children may similarly affect pregnant women considering maternal immunization during pregnancy.”
Because of widespread testing for respiratory viruses at Intermountain facilities, the researchers also could determine that flu vaccine receipt among the mothers did not affect incidence of RSV.
“Our study strengthens the evidence that maternal immunization provides passive protection against influenza to infants during the vulnerable period before they are old enough to receive active immunization,” Dr. Shakib and her associates wrote.
The research was funded by the National Institutes of Health, the University of Utah Children’s Health Research Center and the Pediatric Clinical and Translational Scholar Program, the H.A. and Edna Benning Presidential Endowment, and the University of Utah Center for Clinical and Translational Science through the National Center for Research Resources and the National Center for Advancing Translational Sciences. The authors reported no disclosures.
FROM PEDIATRICS
Vitamin D Supplementation Cuts Dust Mite Atopy
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
AT THE PAS ANNUAL MEETING
Vitamin D supplementation cuts dust mite atopy
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
On Twitter @mitchelzoler
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
On Twitter @mitchelzoler
BALTIMORE – Three months of daily, oral treatment with a relatively high but safe dosage of a vitamin D supplement to pregnant mothers during late gestation followed by continued oral supplementation to their neonates during the first 6 months of life led to a significant reduction in the prevalence of dust-mite skin reactivity in those children once they reached 18 months old in a randomized, controlled trial with 259 mothers and infants.
And in a preliminary assessment that tallied the number of children who required primary care office visits for asthma through age 18 months, children who had received the highest vitamin D supplementation also showed a statistically significant reduction of these visits, compared with the placebo control children, Dr. Cameron C. Grant reported at the annual meeting of the Pediatric Academic Societies.
This suggestion that the vitamin D intervention could cut asthma development is not completely certain because in 18-month-old children, diagnosis of asthma is “very insecure,” noted Dr. Grant, a pediatrician at the University of Auckland, New Zealand and at Starship Children’s Hospital, also in Auckland. In addition, a limitation of the observed effect on dust mite atopy on skin-test challenge was that this follow-up occurred in only 186 (72%) of the 259 infants who participated in the study.
The study’s premise was that vitamin D is an immune system modulator, and that New Zealand provides an excellent setting to test the hypothesis that normalized vitamin D levels can help prevent development of atopy and asthma because many of the country’s residents are vitamin D deficient due to their diet and sun avoidance to prevent skin cancers. Results from prior studies had shown that 57% of New Zealand neonates have inadequate levels of vitamin D at birth, defined as a serum level of 25-hydroxyvitamin D of less than 20 ng/ml (less than 50 nmol/L), Dr. Grant noted.
“I think this intervention will only work in populations that are vitamin D deficient,” Dr. Grant said in an interview. In his study, the average serum level of 25-hydroxyvitamin D among control neonates was 38 nmol/L (about 15 ng/mL). In contrast, neonates born to mothers who had received a daily, higher-dose vitamin D supplement during the third trimester had serum measures that were roughly twice that level.
The study enrolled 260 pregnant women from the Auckland area with a single pregnancy at 26-30 weeks’ gestation; average gestational age at baseline was 27 weeks. Dr. Grant and his associates randomized the mothers to receive 1,000 IU oral vitamin D daily, 2,000 oral vitamin D daily, or placebo. The women delivered 259 infants. Infants born to women on the lower dosage supplement then received 400 IU vitamin daily for 6 months, those born to mothers on the higher level supplement received 800 IU vitamin D daily for 6 months, and those born to mothers in the placebo group received placebo supplements daily for 6 months.
Both supplement regimens led to statistically significant increases in serum levels of 25-hydroxyvitamin D in maternal serum at 36 weeks’ gestation, in cord blood at delivery, in the neonates’ serum at ages 2 months and 4 months, and in infant serum in the higher dosage group at 6 months of age, compared with similar measures taken at all these time points in the placebo group.
In addition, the neonates in the higher dosage group had significantly higher serum levels at 2, 4, and 6 months, compared with the lower dosage group. When measured a final time at 18-month follow-up, a year after the end of vitamin D supplementation, average serum levels of 25-hydroxyvitamin D in an three subgroups of children were virtually identical and similar to maternal serum levels at baseline. Dr. Grant and his associates had previously reported these findings and also had documented the safety of both the low and high levels of vitamin D supplements for both mothers and their children (Pediatrics. 2014 Jan;133[1]:e143-53).
The new findings reported by Dr. Grant focused on clinical outcomes at 18 months. He and his colleagues ran skin-prick testing on 186 of the 259 (72%) children in the study (the remaining children weren’t available for this follow-up assessment). They tested three aeroallergens: cat, pollen, and house dust mite. They saw no significant differences in the prevalence of positive skin-prick reactions among the three study groups to cat and pollen, but prevalence levels of positive reactions to dust mite were 9% in the controls, 3% of children in the low-dosage group, and none in the high dosage group. The difference between the controls and high dosage groups was statistically significant; the difference between the controls and the low dosage group was not significant, Dr. Grant said. Additional testing of specific IgE responses to four different dust mite antigens showed statistically significant reductions in responses to each of the four antigens among the high dosage children, compared with the controls and with the low dosage children.
The researchers also tallied the number of acute, primary care office visits during the first 18 months of life among the children in each of the three subgroups for a variety of respiratory diagnoses. The three groups showed no significant differences in total number of office visits for most of these diagnoses, including colds, otitis media, croup, and bronchitis. However, about 12% of children in the control group had been seen in a primary care office for a diagnosis of asthma, compared with none of the children in the low dosage group and about 4% in the high-dosage group. The differences between the two intervention groups and the control group were statistically significant. Dr. Grant cautioned that this finding is very preliminary and that any conclusions about the impact of vitamin D supplements on asthma incidence must await studies with larger numbers of children who are followed to an older age.
Dr. Grant had no disclosures.
On Twitter @mitchelzoler
AT THE PAS ANNUAL MEETING
Key clinical point: Maternal treatment to achieve adequate vitamin D levels during late gestation followed by neonatal vitamin D supplementation significantly cut dust mite atopy at 18 months of age, along with a suggestion of reduced asthma incidence.
Major finding: Dust mite reactivity at 18 months occurred in no children treated with higher vitamin D supplementation and in 9% of controls.
Data source: A randomized, controlled, single-center study with 260 pregnant women who delivered 259 infants.
Disclosures: Dr. Grant had no disclosures.
Tiotropium inhalation spray effective for asthma regardless of allergic status
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.
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.
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.
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.
EXPERT ANALYSIS FROM THE 2016 AAAAI ANNUAL MEETING
Allergen-specific IgE serologic assays define sensitization, not disease
To the Editor: I read with great interest the commentary by Lau and Naugler1 regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)2 and updated in 2016 (3rd edition) in the I/LA-20 guidance document.3
The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.4 Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease.
Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion5 of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.
While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.
Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.
The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.8 These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.
Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.
Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.
- Lau CK, Naugler C. Serum allergen-specific IgE testing: how much is too much? Cleve Clin J Med 2016; 83;21–24.
- Matsson P, Hamilton RG, Esch RE, et al. Analytical Performance Characteristics and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Second Edition. CLSI document I/LA20-A2. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania USA, 2009
- Hamilton RG, Matsson P, Chan S, et al. Analytical Performance Characteristics, Quality Assurance and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Third Edition. CLSI document I/LA20-A3. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, USA, 2016.
- Hamilton RG. Allergic sensitization is a key risk factor for but not synonymous with allergic disease. J Allergy Clin Immunol 2014; 134:360–361.
- Wians FH Jr. Clinical laboratory tests: which, why and what do the results mean? Lab Medicine 2009; 40:105–113.
- Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol 2015; 15:1–15.
- Sicherer SH, Wood RA, Vickery BP, et al. Impact of allergic reactions on food-specific IgE concentrations and skin test results. J Allergy Clin Immunol Pract. 2015 Dec 21. pii: S2213-2198(15)00658-3. doi: 10.1016/j.jaip.2015.11.015. [Epub ahead of print]
- Hamilton RG. Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds (letter). J Allergy Clin Immunol 2015; 136:811–812.
- Adkinson NF Jr, Hamilton RG. Clinical history-driven diagnosis of allergic diseases: utilizing in vitro IgE testing. Allergy Clin Immunol Pract 2015; 3:871–876.
- Kleine-Tebbe J, Matricardi PM, Hamilton RG. Allergy work-up including component-resolved diagnosis: how to make allergen-specific immunotherapy more specific. Immunol Allergy Clin North Am 2016; 36:191–203.
To the Editor: I read with great interest the commentary by Lau and Naugler1 regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)2 and updated in 2016 (3rd edition) in the I/LA-20 guidance document.3
The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.4 Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease.
Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion5 of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.
While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.
Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.
The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.8 These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.
Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.
Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.
To the Editor: I read with great interest the commentary by Lau and Naugler1 regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)2 and updated in 2016 (3rd edition) in the I/LA-20 guidance document.3
The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.4 Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease.
Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion5 of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.
While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.
Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.
The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.8 These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.
Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.
Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.
- Lau CK, Naugler C. Serum allergen-specific IgE testing: how much is too much? Cleve Clin J Med 2016; 83;21–24.
- Matsson P, Hamilton RG, Esch RE, et al. Analytical Performance Characteristics and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Second Edition. CLSI document I/LA20-A2. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania USA, 2009
- Hamilton RG, Matsson P, Chan S, et al. Analytical Performance Characteristics, Quality Assurance and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Third Edition. CLSI document I/LA20-A3. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, USA, 2016.
- Hamilton RG. Allergic sensitization is a key risk factor for but not synonymous with allergic disease. J Allergy Clin Immunol 2014; 134:360–361.
- Wians FH Jr. Clinical laboratory tests: which, why and what do the results mean? Lab Medicine 2009; 40:105–113.
- Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol 2015; 15:1–15.
- Sicherer SH, Wood RA, Vickery BP, et al. Impact of allergic reactions on food-specific IgE concentrations and skin test results. J Allergy Clin Immunol Pract. 2015 Dec 21. pii: S2213-2198(15)00658-3. doi: 10.1016/j.jaip.2015.11.015. [Epub ahead of print]
- Hamilton RG. Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds (letter). J Allergy Clin Immunol 2015; 136:811–812.
- Adkinson NF Jr, Hamilton RG. Clinical history-driven diagnosis of allergic diseases: utilizing in vitro IgE testing. Allergy Clin Immunol Pract 2015; 3:871–876.
- Kleine-Tebbe J, Matricardi PM, Hamilton RG. Allergy work-up including component-resolved diagnosis: how to make allergen-specific immunotherapy more specific. Immunol Allergy Clin North Am 2016; 36:191–203.
- Lau CK, Naugler C. Serum allergen-specific IgE testing: how much is too much? Cleve Clin J Med 2016; 83;21–24.
- Matsson P, Hamilton RG, Esch RE, et al. Analytical Performance Characteristics and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Second Edition. CLSI document I/LA20-A2. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania USA, 2009
- Hamilton RG, Matsson P, Chan S, et al. Analytical Performance Characteristics, Quality Assurance and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline—Third Edition. CLSI document I/LA20-A3. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, USA, 2016.
- Hamilton RG. Allergic sensitization is a key risk factor for but not synonymous with allergic disease. J Allergy Clin Immunol 2014; 134:360–361.
- Wians FH Jr. Clinical laboratory tests: which, why and what do the results mean? Lab Medicine 2009; 40:105–113.
- Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol 2015; 15:1–15.
- Sicherer SH, Wood RA, Vickery BP, et al. Impact of allergic reactions on food-specific IgE concentrations and skin test results. J Allergy Clin Immunol Pract. 2015 Dec 21. pii: S2213-2198(15)00658-3. doi: 10.1016/j.jaip.2015.11.015. [Epub ahead of print]
- Hamilton RG. Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds (letter). J Allergy Clin Immunol 2015; 136:811–812.
- Adkinson NF Jr, Hamilton RG. Clinical history-driven diagnosis of allergic diseases: utilizing in vitro IgE testing. Allergy Clin Immunol Pract 2015; 3:871–876.
- Kleine-Tebbe J, Matricardi PM, Hamilton RG. Allergy work-up including component-resolved diagnosis: how to make allergen-specific immunotherapy more specific. Immunol Allergy Clin North Am 2016; 36:191–203.
In reply: Allergen-specific IgE serologic assays define sensitization, not disease
In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.
There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.
It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.
In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references.
In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.
There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.
It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.
In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references.
In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.
There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.
It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.
In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references.