Pulmonary Health Hub

Deep suctioning and long lapses between suction treatments were associated with significantly increased lengths of stay in babies hospitalized with bronchiolitis.

Patients who never had deep suctioning stayed a little more than a day, but the length of stay was more than 2 days in patients for whom deep suctioning accounted for 60% or more of their treatments, Dr. Grant M. Mussman and his colleagues reported in the March 4 online issue of JAMA Pediatrics (2013[doi:10.1001/jamapediatrics.2013.36]).

Similarly, patients who experienced several lapses of 4 hours between treatments were hospitalized significantly longer than were those with no treatment lapses (mean of 2.3 days vs. 1.7 days).

Compared with a noninvasive nasal-type suction device, deep suctioning may aggravate the bronchial swelling and mucus sloughing that already causes breathing problems in these tiny patients, wrote Dr. Mussman of Cincinnati Children’s Hospital Medical Center.

"[It] may be that deep suctioning causes edema and irritation of the upper airway. Alternatively, noninvasive suctioning could be more effective in mobilizing nasal secretions through the larger caliber catheter."

Regular treatments with no lapses probably keep the airways open more consistently, they noted. "It is also possible that regular suctioning results in agitation of the patient, with resultant increased minute volume and secretion mobilization, resulting in shorter length of stay."

The study cohort consisted of 740 patients who were studied for device type (deep or noninvasive), 695 of which were studied for treatment timing. The patients were a mean of 6 months old, and all had been hospitalized for bronchiolitis.

Deep suction was defined as the insertion of a nasopharyngeal catheter, and noninvasive as the use of nasal-type aspirators, excluding bulb syringe. The exposure was the percentage of treatments that used deep suctioning (0%-35%; more than 35%-60%; and more then 60%).

The adjusted mean length of stay for infants who had no deep suctioning was 1.75 days. The stay was 1.91 days for those with up to 35% deep suctioning, 1.96 days for more than 35%-60% deep suctioning, and 2.35 days for more than 60% deep suctioning.

For the suction treatment timing group, a suctioning lapse was defined as two sequential suctioning events separated by more than 4 hours during the first 24 hours of admission. The investigators said that the 4-hour increment is the most common reassessment timing.

Infants with no treatment lapses had a mean adjusted hospital stay of 1.62 days. In contrast, the mean length of stay was 1.72 days for infants with one treatment lapse, 2.09 days for those with two lapses, and 2.64 days for those with three or four lapses.

"We believe the difference in geometric mean of up to 1 day between patients with no suctioning lapses and those with three or four lapses is clinically meaningful," the authors noted. However, "Because there is insufficient data to determine a causal relationship, we intend to continue to examine these associations as we incorporate these findings into clinical practice at our institution."

Dr. Mussman had no relevant financial disclosures.

michele.sullivan@frontlinemedcom.com

Deep suctioning and long lapses between suction treatments were associated with significantly increased lengths of stay in babies hospitalized with bronchiolitis.

Patients who never had deep suctioning stayed a little more than a day, but the length of stay was more than 2 days in patients for whom deep suctioning accounted for 60% or more of their treatments, Dr. Grant M. Mussman and his colleagues reported in the March 4 online issue of JAMA Pediatrics (2013[doi:10.1001/jamapediatrics.2013.36]).

Similarly, patients who experienced several lapses of 4 hours between treatments were hospitalized significantly longer than were those with no treatment lapses (mean of 2.3 days vs. 1.7 days).

Compared with a noninvasive nasal-type suction device, deep suctioning may aggravate the bronchial swelling and mucus sloughing that already causes breathing problems in these tiny patients, wrote Dr. Mussman of Cincinnati Children’s Hospital Medical Center.

"[It] may be that deep suctioning causes edema and irritation of the upper airway. Alternatively, noninvasive suctioning could be more effective in mobilizing nasal secretions through the larger caliber catheter."

Regular treatments with no lapses probably keep the airways open more consistently, they noted. "It is also possible that regular suctioning results in agitation of the patient, with resultant increased minute volume and secretion mobilization, resulting in shorter length of stay."

The study cohort consisted of 740 patients who were studied for device type (deep or noninvasive), 695 of which were studied for treatment timing. The patients were a mean of 6 months old, and all had been hospitalized for bronchiolitis.

Deep suction was defined as the insertion of a nasopharyngeal catheter, and noninvasive as the use of nasal-type aspirators, excluding bulb syringe. The exposure was the percentage of treatments that used deep suctioning (0%-35%; more than 35%-60%; and more then 60%).

The adjusted mean length of stay for infants who had no deep suctioning was 1.75 days. The stay was 1.91 days for those with up to 35% deep suctioning, 1.96 days for more than 35%-60% deep suctioning, and 2.35 days for more than 60% deep suctioning.

For the suction treatment timing group, a suctioning lapse was defined as two sequential suctioning events separated by more than 4 hours during the first 24 hours of admission. The investigators said that the 4-hour increment is the most common reassessment timing.

Infants with no treatment lapses had a mean adjusted hospital stay of 1.62 days. In contrast, the mean length of stay was 1.72 days for infants with one treatment lapse, 2.09 days for those with two lapses, and 2.64 days for those with three or four lapses.

"We believe the difference in geometric mean of up to 1 day between patients with no suctioning lapses and those with three or four lapses is clinically meaningful," the authors noted. However, "Because there is insufficient data to determine a causal relationship, we intend to continue to examine these associations as we incorporate these findings into clinical practice at our institution."

Dr. Mussman had no relevant financial disclosures.

michele.sullivan@frontlinemedcom.com

Deep suctioning and long lapses between suction treatments were associated with significantly increased lengths of stay in babies hospitalized with bronchiolitis.

Patients who never had deep suctioning stayed a little more than a day, but the length of stay was more than 2 days in patients for whom deep suctioning accounted for 60% or more of their treatments, Dr. Grant M. Mussman and his colleagues reported in the March 4 online issue of JAMA Pediatrics (2013[doi:10.1001/jamapediatrics.2013.36]).

Similarly, patients who experienced several lapses of 4 hours between treatments were hospitalized significantly longer than were those with no treatment lapses (mean of 2.3 days vs. 1.7 days).

Compared with a noninvasive nasal-type suction device, deep suctioning may aggravate the bronchial swelling and mucus sloughing that already causes breathing problems in these tiny patients, wrote Dr. Mussman of Cincinnati Children’s Hospital Medical Center.

"[It] may be that deep suctioning causes edema and irritation of the upper airway. Alternatively, noninvasive suctioning could be more effective in mobilizing nasal secretions through the larger caliber catheter."

Regular treatments with no lapses probably keep the airways open more consistently, they noted. "It is also possible that regular suctioning results in agitation of the patient, with resultant increased minute volume and secretion mobilization, resulting in shorter length of stay."

The study cohort consisted of 740 patients who were studied for device type (deep or noninvasive), 695 of which were studied for treatment timing. The patients were a mean of 6 months old, and all had been hospitalized for bronchiolitis.

Deep suction was defined as the insertion of a nasopharyngeal catheter, and noninvasive as the use of nasal-type aspirators, excluding bulb syringe. The exposure was the percentage of treatments that used deep suctioning (0%-35%; more than 35%-60%; and more then 60%).

The adjusted mean length of stay for infants who had no deep suctioning was 1.75 days. The stay was 1.91 days for those with up to 35% deep suctioning, 1.96 days for more than 35%-60% deep suctioning, and 2.35 days for more than 60% deep suctioning.

For the suction treatment timing group, a suctioning lapse was defined as two sequential suctioning events separated by more than 4 hours during the first 24 hours of admission. The investigators said that the 4-hour increment is the most common reassessment timing.

Infants with no treatment lapses had a mean adjusted hospital stay of 1.62 days. In contrast, the mean length of stay was 1.72 days for infants with one treatment lapse, 2.09 days for those with two lapses, and 2.64 days for those with three or four lapses.

"We believe the difference in geometric mean of up to 1 day between patients with no suctioning lapses and those with three or four lapses is clinically meaningful," the authors noted. However, "Because there is insufficient data to determine a causal relationship, we intend to continue to examine these associations as we incorporate these findings into clinical practice at our institution."

Dr. Mussman had no relevant financial disclosures.

michele.sullivan@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

Most likely I am not alone with the feeling that we spend a lot of resources diagnosing sleep apnea, meticulously titrating CPAP devices, and patiently listening to some of our patients as they list the reasons for not using it.

Many times, the patients have been back to the sleep specialists, who try in earnest to make it work because we all know the litany of potential adverse downstream effects if apnea is left untreated.

We all also know that frightening our patients ("untreated sleep apnea can increase the risk for sudden cardiac death and heart failure. ...") into CPAP compliance is ineffective. So, for the lucky patients whose insurance coverage facilitates the fitting of oral appliances, such as the mandibular advancement device (MAD), we can try these.

Although the reduction in overall apneic episodes is less with MAD than with CPAP devices, the adherence to the MAD may be higher.

So how do CPAP and oral appliances fare head-to-head?

Australian investigators conducted a randomized controlled clinical trial evaluating the health outcomes of patients using the MAD or CPAP for obstructive sleep apnea (Am. J. Respir. Crit. Care Med. Feb. 14, 2013 [doi:10.1164/rccm.201212-2223OC]).

In this study, 126 patients with moderate to severe OSA were randomly assigned to use of MAD or CPAP for 1 month. Patients were excluded if they had central sleep apnea, need for immediate treatment, a coexisting sleep disorder, regular use of sedatives or narcotics, or pre-existing lung or psychiatric disease.

The primary outcome was a difference in 24-hour mean arterial blood pressure. Secondary outcomes included cardiovascular events and arterial stiffness. Neurobehavioral function and quality of life also were measured.

CPAP was significantly more effective than MAD for reducing the apnea-hypopnea index (AHI), but compliance was significantly greater with MAD (6.5 hours per night vs. 5.2 hours per night). No differences in the 24-hour mean arterial pressure were observed, though neither treatment improved blood pressure. Sleepiness, driving stimulator performance, and disease-specific quality of life improved with both treatments by similar amounts. MAD was superior to CPAP on several quality-of-life domains.

This study is extremely informative for our practices in which we cannot consistently provide either motivational enhancement or interventions to improve adherence with CPAP. For CPAP-nonadherent patients for whom an appliance seems like an appropriate next step, this should be pursued. In the case of sleep apnea, we should not let perfect be the enemy of good.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

Most likely I am not alone with the feeling that we spend a lot of resources diagnosing sleep apnea, meticulously titrating CPAP devices, and patiently listening to some of our patients as they list the reasons for not using it.

Many times, the patients have been back to the sleep specialists, who try in earnest to make it work because we all know the litany of potential adverse downstream effects if apnea is left untreated.

We all also know that frightening our patients ("untreated sleep apnea can increase the risk for sudden cardiac death and heart failure. ...") into CPAP compliance is ineffective. So, for the lucky patients whose insurance coverage facilitates the fitting of oral appliances, such as the mandibular advancement device (MAD), we can try these.

Although the reduction in overall apneic episodes is less with MAD than with CPAP devices, the adherence to the MAD may be higher.

So how do CPAP and oral appliances fare head-to-head?

Australian investigators conducted a randomized controlled clinical trial evaluating the health outcomes of patients using the MAD or CPAP for obstructive sleep apnea (Am. J. Respir. Crit. Care Med. Feb. 14, 2013 [doi:10.1164/rccm.201212-2223OC]).

In this study, 126 patients with moderate to severe OSA were randomly assigned to use of MAD or CPAP for 1 month. Patients were excluded if they had central sleep apnea, need for immediate treatment, a coexisting sleep disorder, regular use of sedatives or narcotics, or pre-existing lung or psychiatric disease.

The primary outcome was a difference in 24-hour mean arterial blood pressure. Secondary outcomes included cardiovascular events and arterial stiffness. Neurobehavioral function and quality of life also were measured.

CPAP was significantly more effective than MAD for reducing the apnea-hypopnea index (AHI), but compliance was significantly greater with MAD (6.5 hours per night vs. 5.2 hours per night). No differences in the 24-hour mean arterial pressure were observed, though neither treatment improved blood pressure. Sleepiness, driving stimulator performance, and disease-specific quality of life improved with both treatments by similar amounts. MAD was superior to CPAP on several quality-of-life domains.

This study is extremely informative for our practices in which we cannot consistently provide either motivational enhancement or interventions to improve adherence with CPAP. For CPAP-nonadherent patients for whom an appliance seems like an appropriate next step, this should be pursued. In the case of sleep apnea, we should not let perfect be the enemy of good.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

Most likely I am not alone with the feeling that we spend a lot of resources diagnosing sleep apnea, meticulously titrating CPAP devices, and patiently listening to some of our patients as they list the reasons for not using it.

Many times, the patients have been back to the sleep specialists, who try in earnest to make it work because we all know the litany of potential adverse downstream effects if apnea is left untreated.

We all also know that frightening our patients ("untreated sleep apnea can increase the risk for sudden cardiac death and heart failure. ...") into CPAP compliance is ineffective. So, for the lucky patients whose insurance coverage facilitates the fitting of oral appliances, such as the mandibular advancement device (MAD), we can try these.

Although the reduction in overall apneic episodes is less with MAD than with CPAP devices, the adherence to the MAD may be higher.

So how do CPAP and oral appliances fare head-to-head?

Australian investigators conducted a randomized controlled clinical trial evaluating the health outcomes of patients using the MAD or CPAP for obstructive sleep apnea (Am. J. Respir. Crit. Care Med. Feb. 14, 2013 [doi:10.1164/rccm.201212-2223OC]).

In this study, 126 patients with moderate to severe OSA were randomly assigned to use of MAD or CPAP for 1 month. Patients were excluded if they had central sleep apnea, need for immediate treatment, a coexisting sleep disorder, regular use of sedatives or narcotics, or pre-existing lung or psychiatric disease.

The primary outcome was a difference in 24-hour mean arterial blood pressure. Secondary outcomes included cardiovascular events and arterial stiffness. Neurobehavioral function and quality of life also were measured.

CPAP was significantly more effective than MAD for reducing the apnea-hypopnea index (AHI), but compliance was significantly greater with MAD (6.5 hours per night vs. 5.2 hours per night). No differences in the 24-hour mean arterial pressure were observed, though neither treatment improved blood pressure. Sleepiness, driving stimulator performance, and disease-specific quality of life improved with both treatments by similar amounts. MAD was superior to CPAP on several quality-of-life domains.

This study is extremely informative for our practices in which we cannot consistently provide either motivational enhancement or interventions to improve adherence with CPAP. For CPAP-nonadherent patients for whom an appliance seems like an appropriate next step, this should be pursued. In the case of sleep apnea, we should not let perfect be the enemy of good.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at imnews@elsevier.com.

ILLUSTRATIVE CASE

A mother brings in her 18-month-old son because he’s had a runny nose and low-grade fever for the past 4 days—and a cough that kept them both up last night. You diagnose a viral URI, and she requests a strong cough medicine so he (and she) can get a good night’s sleep. What can you recommend that is both safe and effective for a child of this age?

For primary care physicians, office visits for coughing kids with URIs are commonplace. In addition to the cost of such visits, Americans spend some $3.5 billion a year on over-the-counter (OTC) cough and cold remedies, and often give them to young children.

It’s not enough to tell parents what not to do
As physicians (and parents), we understand the desire to give a coughing child something to ease the symptoms. We also know that OTC cough and cold medications can lead to serious complications, and even death. Between 1983 and 2007, 118 pediatric deaths were attributed to the misuse of such preparations.² And, in a 3-year span (2005-2008), the American Association of Poison Control Centers received 64,658 calls for exposures to cough and cold remedies in children younger than 2 years of age, 28 of which resulted in a major adverse reaction or death.³

The US Food and Drug Administration recommends against the use of OTC cough and cold medications in children younger than 2 years,⁴ and the American Academy of Pediatrics has issued strict warnings about the use of OTC cough and cold preparations in children younger than 6 years.⁵ But warning parents of the dangers of giving them to young children without offering an alternative doesn’t satisfy anyone’s needs, and many parents continue to use these medications.

What about honey?
A study published in 2007 evaluated buckwheat honey and found it to be superior to no treatment and equal to honey-flavored dextromethorphan in reducing cough severity and improving sleep for children and their parents.⁶ Honey is known to have both antioxidant and antimicrobial properties—a possible scientific explanation for its effect. Before recommending honey for kids with URIs, however, more evidence of its efficacy was needed.

STUDY SUMMARY: Honey reduces cough frequency and severity

Cohen et al sought to determine whether honey, administered before bedtime, would decrease coughing in children between the ages of one and 5 years—and improve sleep for both the children and their caregivers.¹ They enrolled 300 children with a nocturnal cough of <7 days’ duration and a diagnosis of URI in a one-night study.

Children were excluded if they had any signs or symptoms of asthma, pneumonia, sinusitis, allergic rhinitis, or laryngotracheobronchitis, or if they had been given any cough remedy, including honey, the night before. Parents completed a 5-question survey, using a 7-point Likert scale to assess the child’s cough and both the child’s and parents’ sleep the previous night. Only children whose parents rated their child’s cough severity ≥3 in 2 of the 3 questions related to cough were included in the trial.

The study had a double-blind randomized design, with 4 treatment arms. Three groups received 10 g (about 1.5 tsp) of one of 3 types of honey: eucalyptus, citrus, or labiatae (derived from plants including sage, mint, and thyme); the fourth group received a placebo of silan date extract, which is similar to honey in color, texture, and taste.

Children in all 4 groups received the preparation 30 minutes before bedtime. Neither the parents nor the physicians or study coordinators knew which preparation the children received. The following day, research assistants telephoned the parent who had completed the initial survey and asked the same 5 questions. The primary outcome measure was the change in cough frequency from the night before to the night after treatment. Secondary measures included cough severity and the effect on sleep for both the child and the parent.

Of the 300 children initially enrolled, 270 (90%) completed the trial, with an even distribution among the groups. While there were improvements across all outcomes for both the treatment and placebo groups, the changes were statistically significant only in the treatment groups. There were no significant differences in efficacy noted among the 3 types of honey. Adverse effects of stomachache, nausea, or vomiting were noted by 4 parents in the treatment groups and one in the placebo group, a difference that was not statistically significant.

WHAT’S NEW?: We have more evidence of honey’s efficacy

For children older than one year with a viral URI, we can now recommend 1.5 tsp honey to be given prior to bedtime as a cough remedy. This may reduce the use of potentially harmful and often ineffective OTC cough and cold remedies.

CAVEATS: Honey is unsafe for the youngest children

An obvious limitation of this study was its brevity. Although one night of improved cough and sleep is important, a study that showed honey’s sustained benefit as a cough suppressant would be more convincing. What’s more, there are safety concerns that are age-related.

Honey is considered unsafe for children younger than one year because of the risk of botulism. And honey has the potential to increase dental caries if it is given nightly for a prolonged period of time.

We do not know whether all varieties of honey will have the same benefit, and the source of store-bought honey is not always identified. The authors of this study received funding from the Honey Board of Israel.

CHALLENGES TO IMPLEMENTATION: Parents may be reluctant to abandon OTCs

Changing the behavior of parents and other caregivers who are accustomed to treating children with OTC cough and cold remedies is likely to be an uphill battle. Because honey is readily available, however—often as close as the pantry—and perceived to be safe and nutritious, a recommendation from a trusted physician could go a long way toward its implementation.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A mother brings in her 18-month-old son because he’s had a runny nose and low-grade fever for the past 4 days—and a cough that kept them both up last night. You diagnose a viral URI, and she requests a strong cough medicine so he (and she) can get a good night’s sleep. What can you recommend that is both safe and effective for a child of this age?

For primary care physicians, office visits for coughing kids with URIs are commonplace. In addition to the cost of such visits, Americans spend some $3.5 billion a year on over-the-counter (OTC) cough and cold remedies, and often give them to young children.

It’s not enough to tell parents what not to do
As physicians (and parents), we understand the desire to give a coughing child something to ease the symptoms. We also know that OTC cough and cold medications can lead to serious complications, and even death. Between 1983 and 2007, 118 pediatric deaths were attributed to the misuse of such preparations.² And, in a 3-year span (2005-2008), the American Association of Poison Control Centers received 64,658 calls for exposures to cough and cold remedies in children younger than 2 years of age, 28 of which resulted in a major adverse reaction or death.³

The US Food and Drug Administration recommends against the use of OTC cough and cold medications in children younger than 2 years,⁴ and the American Academy of Pediatrics has issued strict warnings about the use of OTC cough and cold preparations in children younger than 6 years.⁵ But warning parents of the dangers of giving them to young children without offering an alternative doesn’t satisfy anyone’s needs, and many parents continue to use these medications.

What about honey?
A study published in 2007 evaluated buckwheat honey and found it to be superior to no treatment and equal to honey-flavored dextromethorphan in reducing cough severity and improving sleep for children and their parents.⁶ Honey is known to have both antioxidant and antimicrobial properties—a possible scientific explanation for its effect. Before recommending honey for kids with URIs, however, more evidence of its efficacy was needed.

STUDY SUMMARY: Honey reduces cough frequency and severity

Cohen et al sought to determine whether honey, administered before bedtime, would decrease coughing in children between the ages of one and 5 years—and improve sleep for both the children and their caregivers.¹ They enrolled 300 children with a nocturnal cough of <7 days’ duration and a diagnosis of URI in a one-night study.

Children were excluded if they had any signs or symptoms of asthma, pneumonia, sinusitis, allergic rhinitis, or laryngotracheobronchitis, or if they had been given any cough remedy, including honey, the night before. Parents completed a 5-question survey, using a 7-point Likert scale to assess the child’s cough and both the child’s and parents’ sleep the previous night. Only children whose parents rated their child’s cough severity ≥3 in 2 of the 3 questions related to cough were included in the trial.

The study had a double-blind randomized design, with 4 treatment arms. Three groups received 10 g (about 1.5 tsp) of one of 3 types of honey: eucalyptus, citrus, or labiatae (derived from plants including sage, mint, and thyme); the fourth group received a placebo of silan date extract, which is similar to honey in color, texture, and taste.

Children in all 4 groups received the preparation 30 minutes before bedtime. Neither the parents nor the physicians or study coordinators knew which preparation the children received. The following day, research assistants telephoned the parent who had completed the initial survey and asked the same 5 questions. The primary outcome measure was the change in cough frequency from the night before to the night after treatment. Secondary measures included cough severity and the effect on sleep for both the child and the parent.

Of the 300 children initially enrolled, 270 (90%) completed the trial, with an even distribution among the groups. While there were improvements across all outcomes for both the treatment and placebo groups, the changes were statistically significant only in the treatment groups. There were no significant differences in efficacy noted among the 3 types of honey. Adverse effects of stomachache, nausea, or vomiting were noted by 4 parents in the treatment groups and one in the placebo group, a difference that was not statistically significant.

WHAT’S NEW?: We have more evidence of honey’s efficacy

For children older than one year with a viral URI, we can now recommend 1.5 tsp honey to be given prior to bedtime as a cough remedy. This may reduce the use of potentially harmful and often ineffective OTC cough and cold remedies.

CAVEATS: Honey is unsafe for the youngest children

An obvious limitation of this study was its brevity. Although one night of improved cough and sleep is important, a study that showed honey’s sustained benefit as a cough suppressant would be more convincing. What’s more, there are safety concerns that are age-related.

Honey is considered unsafe for children younger than one year because of the risk of botulism. And honey has the potential to increase dental caries if it is given nightly for a prolonged period of time.

We do not know whether all varieties of honey will have the same benefit, and the source of store-bought honey is not always identified. The authors of this study received funding from the Honey Board of Israel.

CHALLENGES TO IMPLEMENTATION: Parents may be reluctant to abandon OTCs

Changing the behavior of parents and other caregivers who are accustomed to treating children with OTC cough and cold remedies is likely to be an uphill battle. Because honey is readily available, however—often as close as the pantry—and perceived to be safe and nutritious, a recommendation from a trusted physician could go a long way toward its implementation.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A mother brings in her 18-month-old son because he’s had a runny nose and low-grade fever for the past 4 days—and a cough that kept them both up last night. You diagnose a viral URI, and she requests a strong cough medicine so he (and she) can get a good night’s sleep. What can you recommend that is both safe and effective for a child of this age?

For primary care physicians, office visits for coughing kids with URIs are commonplace. In addition to the cost of such visits, Americans spend some $3.5 billion a year on over-the-counter (OTC) cough and cold remedies, and often give them to young children.

It’s not enough to tell parents what not to do
As physicians (and parents), we understand the desire to give a coughing child something to ease the symptoms. We also know that OTC cough and cold medications can lead to serious complications, and even death. Between 1983 and 2007, 118 pediatric deaths were attributed to the misuse of such preparations.² And, in a 3-year span (2005-2008), the American Association of Poison Control Centers received 64,658 calls for exposures to cough and cold remedies in children younger than 2 years of age, 28 of which resulted in a major adverse reaction or death.³

The US Food and Drug Administration recommends against the use of OTC cough and cold medications in children younger than 2 years,⁴ and the American Academy of Pediatrics has issued strict warnings about the use of OTC cough and cold preparations in children younger than 6 years.⁵ But warning parents of the dangers of giving them to young children without offering an alternative doesn’t satisfy anyone’s needs, and many parents continue to use these medications.

What about honey?
A study published in 2007 evaluated buckwheat honey and found it to be superior to no treatment and equal to honey-flavored dextromethorphan in reducing cough severity and improving sleep for children and their parents.⁶ Honey is known to have both antioxidant and antimicrobial properties—a possible scientific explanation for its effect. Before recommending honey for kids with URIs, however, more evidence of its efficacy was needed.

STUDY SUMMARY: Honey reduces cough frequency and severity

Cohen et al sought to determine whether honey, administered before bedtime, would decrease coughing in children between the ages of one and 5 years—and improve sleep for both the children and their caregivers.¹ They enrolled 300 children with a nocturnal cough of <7 days’ duration and a diagnosis of URI in a one-night study.

Children were excluded if they had any signs or symptoms of asthma, pneumonia, sinusitis, allergic rhinitis, or laryngotracheobronchitis, or if they had been given any cough remedy, including honey, the night before. Parents completed a 5-question survey, using a 7-point Likert scale to assess the child’s cough and both the child’s and parents’ sleep the previous night. Only children whose parents rated their child’s cough severity ≥3 in 2 of the 3 questions related to cough were included in the trial.

The study had a double-blind randomized design, with 4 treatment arms. Three groups received 10 g (about 1.5 tsp) of one of 3 types of honey: eucalyptus, citrus, or labiatae (derived from plants including sage, mint, and thyme); the fourth group received a placebo of silan date extract, which is similar to honey in color, texture, and taste.

Children in all 4 groups received the preparation 30 minutes before bedtime. Neither the parents nor the physicians or study coordinators knew which preparation the children received. The following day, research assistants telephoned the parent who had completed the initial survey and asked the same 5 questions. The primary outcome measure was the change in cough frequency from the night before to the night after treatment. Secondary measures included cough severity and the effect on sleep for both the child and the parent.

Of the 300 children initially enrolled, 270 (90%) completed the trial, with an even distribution among the groups. While there were improvements across all outcomes for both the treatment and placebo groups, the changes were statistically significant only in the treatment groups. There were no significant differences in efficacy noted among the 3 types of honey. Adverse effects of stomachache, nausea, or vomiting were noted by 4 parents in the treatment groups and one in the placebo group, a difference that was not statistically significant.

WHAT’S NEW?: We have more evidence of honey’s efficacy

For children older than one year with a viral URI, we can now recommend 1.5 tsp honey to be given prior to bedtime as a cough remedy. This may reduce the use of potentially harmful and often ineffective OTC cough and cold remedies.

CAVEATS: Honey is unsafe for the youngest children

An obvious limitation of this study was its brevity. Although one night of improved cough and sleep is important, a study that showed honey’s sustained benefit as a cough suppressant would be more convincing. What’s more, there are safety concerns that are age-related.

Honey is considered unsafe for children younger than one year because of the risk of botulism. And honey has the potential to increase dental caries if it is given nightly for a prolonged period of time.

We do not know whether all varieties of honey will have the same benefit, and the source of store-bought honey is not always identified. The authors of this study received funding from the Honey Board of Israel.

CHALLENGES TO IMPLEMENTATION: Parents may be reluctant to abandon OTCs

Changing the behavior of parents and other caregivers who are accustomed to treating children with OTC cough and cold remedies is likely to be an uphill battle. Because honey is readily available, however—often as close as the pantry—and perceived to be safe and nutritious, a recommendation from a trusted physician could go a long way toward its implementation.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

The sensitivity and specificity of a diagnostic test that rapidly detects tuberculosis support its use as an initial diagnostic test in adults suspected of having TB, including multidrug- resistant or HIV-associated disease, based on a meta-analysis of studies evaluating the test, researchers say.

In addition, the meta-analysis results suggest that the test, the Xpert assay, "may also be valuable as an add-on test following a negative smear microscopy result in patients suspected of having TB," said Karen Steingart, of the University of Washington School of Public Health, Seattle, and her associates. The researchers were from the Cochrane Infectious Diseases Group; McGill University, Montreal; and the Foundation for Innovative New Diagnostics (FIND), Geneva. The study was published in the Cochrane Database of Systematic Reviews (doi:10.1002/14651858.CD009593.pub2).

Photo Credit: Janice Carr, Centers for Disease Control and Prevention

Xpert, manufactured by Cepheid Inc., is an automated polymerase chain reaction test that detects Mycobacterium tuberculosis complex and rifampin resistance within two hours using a sputum sample, used outside of a reference lab "with minimal hands-on technical time," as opposed to conventional sputum smear microscopy, which is cheaper, but requires a microscope in a lab and does not detect drug resistance.

In 2010, Xpert was endorsed by the World Health Organization for use as the initial diagnostic test on people suspected of having MDR-TB or HIV-associated TB. That year, WHO reported that there were 8.8 million new cases of TB worldwide; and that 1.1 million people who did not have HIV and 350,000 people with HIV died of TB.

The study reviewed 18 studies of more than 7,500 adults, mostly in low and middle-income countries, with a high burden of TB, which evaluated the test as an initial test used as a replacement for microscopy, and as an add-on test when a microscopy smear was negative, in adults suspected of having in pulmonary TB, or multidrug-resistant TB, with or without HIV infection.

The main results of the test are as follows:

• A "modest" sensitivity of 88% and a "high" specificity of 98% for detecting TB when used it as an initial test that replaced smear microscopy.

• A sensitivity of 67% and a specificity of 98% when used as an add-on follow-up test to detect TB, after a negative smear microscopy.

• A sensitivity of 80% for detecting TB in people with HIV and 89% in people without HIV.

•A sensitivity of 94% and a specificity of 98% for detecting rifampin resistance (an indicator of multidrug resistances) when used as a replacement for culture based-drug susceptibility testing

The rate of indeterminate results was a "very low" 1%, they said.

The results "lend support to the WHO recommendation on the use of Xpert as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having MDR-TB or HIV-associated TB," the authors concluded. Future studies should include those that evaluate the results of the test in children, as those data are starting to accumulate, and result of the test in different settings, such as TB screening centers and antiretroviral clinics, they added.

The review "provides high quality evidence that reinforces WHO’s endorsement of this test," Dr. Karin Weyer, the coordinator of Diagnostics and Drug Resistance Laboratories at WHO, said in a written statement. "Recent price reductions have greatly facilitated roll-out of this technology," with 1.4 million test cartridges and the instruments needed to perform the test to be distributed in 21 countries with a high TB burden, she added.

In the United States, TB has been declining, since a peak in 1992, with 10,528 TB cases reported in 2011, almost a 6% drop from the number of reports in 2010, according to the Centers for Disease Control and Prevention. In 2009, the last year mortality data are available, there were 529 TB deaths, a 10% drop from 2008, when there were 590 deaths.

The editorial base of the Cochrane Infectious Diseases Group (CIDG), which provided part of the funding for the review, is funded by the U.K. Department for International Development "for the benefit of developing countries." One study author disclosed having conducted studies and published on the Xpert test in a project with FIND, Cepheid, and academic partners. Others reported having no relevant financial conflicts.

e.mechcatie@elsevier.com

The sensitivity and specificity of a diagnostic test that rapidly detects tuberculosis support its use as an initial diagnostic test in adults suspected of having TB, including multidrug- resistant or HIV-associated disease, based on a meta-analysis of studies evaluating the test, researchers say.

In addition, the meta-analysis results suggest that the test, the Xpert assay, "may also be valuable as an add-on test following a negative smear microscopy result in patients suspected of having TB," said Karen Steingart, of the University of Washington School of Public Health, Seattle, and her associates. The researchers were from the Cochrane Infectious Diseases Group; McGill University, Montreal; and the Foundation for Innovative New Diagnostics (FIND), Geneva. The study was published in the Cochrane Database of Systematic Reviews (doi:10.1002/14651858.CD009593.pub2).

Photo Credit: Janice Carr, Centers for Disease Control and Prevention

Xpert, manufactured by Cepheid Inc., is an automated polymerase chain reaction test that detects Mycobacterium tuberculosis complex and rifampin resistance within two hours using a sputum sample, used outside of a reference lab "with minimal hands-on technical time," as opposed to conventional sputum smear microscopy, which is cheaper, but requires a microscope in a lab and does not detect drug resistance.

In 2010, Xpert was endorsed by the World Health Organization for use as the initial diagnostic test on people suspected of having MDR-TB or HIV-associated TB. That year, WHO reported that there were 8.8 million new cases of TB worldwide; and that 1.1 million people who did not have HIV and 350,000 people with HIV died of TB.

The study reviewed 18 studies of more than 7,500 adults, mostly in low and middle-income countries, with a high burden of TB, which evaluated the test as an initial test used as a replacement for microscopy, and as an add-on test when a microscopy smear was negative, in adults suspected of having in pulmonary TB, or multidrug-resistant TB, with or without HIV infection.

The main results of the test are as follows:

• A "modest" sensitivity of 88% and a "high" specificity of 98% for detecting TB when used it as an initial test that replaced smear microscopy.

• A sensitivity of 67% and a specificity of 98% when used as an add-on follow-up test to detect TB, after a negative smear microscopy.

• A sensitivity of 80% for detecting TB in people with HIV and 89% in people without HIV.

•A sensitivity of 94% and a specificity of 98% for detecting rifampin resistance (an indicator of multidrug resistances) when used as a replacement for culture based-drug susceptibility testing

The rate of indeterminate results was a "very low" 1%, they said.

The results "lend support to the WHO recommendation on the use of Xpert as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having MDR-TB or HIV-associated TB," the authors concluded. Future studies should include those that evaluate the results of the test in children, as those data are starting to accumulate, and result of the test in different settings, such as TB screening centers and antiretroviral clinics, they added.

The review "provides high quality evidence that reinforces WHO’s endorsement of this test," Dr. Karin Weyer, the coordinator of Diagnostics and Drug Resistance Laboratories at WHO, said in a written statement. "Recent price reductions have greatly facilitated roll-out of this technology," with 1.4 million test cartridges and the instruments needed to perform the test to be distributed in 21 countries with a high TB burden, she added.

In the United States, TB has been declining, since a peak in 1992, with 10,528 TB cases reported in 2011, almost a 6% drop from the number of reports in 2010, according to the Centers for Disease Control and Prevention. In 2009, the last year mortality data are available, there were 529 TB deaths, a 10% drop from 2008, when there were 590 deaths.

The editorial base of the Cochrane Infectious Diseases Group (CIDG), which provided part of the funding for the review, is funded by the U.K. Department for International Development "for the benefit of developing countries." One study author disclosed having conducted studies and published on the Xpert test in a project with FIND, Cepheid, and academic partners. Others reported having no relevant financial conflicts.

e.mechcatie@elsevier.com

The sensitivity and specificity of a diagnostic test that rapidly detects tuberculosis support its use as an initial diagnostic test in adults suspected of having TB, including multidrug- resistant or HIV-associated disease, based on a meta-analysis of studies evaluating the test, researchers say.

In addition, the meta-analysis results suggest that the test, the Xpert assay, "may also be valuable as an add-on test following a negative smear microscopy result in patients suspected of having TB," said Karen Steingart, of the University of Washington School of Public Health, Seattle, and her associates. The researchers were from the Cochrane Infectious Diseases Group; McGill University, Montreal; and the Foundation for Innovative New Diagnostics (FIND), Geneva. The study was published in the Cochrane Database of Systematic Reviews (doi:10.1002/14651858.CD009593.pub2).

Photo Credit: Janice Carr, Centers for Disease Control and Prevention

Xpert, manufactured by Cepheid Inc., is an automated polymerase chain reaction test that detects Mycobacterium tuberculosis complex and rifampin resistance within two hours using a sputum sample, used outside of a reference lab "with minimal hands-on technical time," as opposed to conventional sputum smear microscopy, which is cheaper, but requires a microscope in a lab and does not detect drug resistance.

In 2010, Xpert was endorsed by the World Health Organization for use as the initial diagnostic test on people suspected of having MDR-TB or HIV-associated TB. That year, WHO reported that there were 8.8 million new cases of TB worldwide; and that 1.1 million people who did not have HIV and 350,000 people with HIV died of TB.

The study reviewed 18 studies of more than 7,500 adults, mostly in low and middle-income countries, with a high burden of TB, which evaluated the test as an initial test used as a replacement for microscopy, and as an add-on test when a microscopy smear was negative, in adults suspected of having in pulmonary TB, or multidrug-resistant TB, with or without HIV infection.

The main results of the test are as follows:

• A "modest" sensitivity of 88% and a "high" specificity of 98% for detecting TB when used it as an initial test that replaced smear microscopy.

• A sensitivity of 67% and a specificity of 98% when used as an add-on follow-up test to detect TB, after a negative smear microscopy.

• A sensitivity of 80% for detecting TB in people with HIV and 89% in people without HIV.

•A sensitivity of 94% and a specificity of 98% for detecting rifampin resistance (an indicator of multidrug resistances) when used as a replacement for culture based-drug susceptibility testing

The rate of indeterminate results was a "very low" 1%, they said.

The results "lend support to the WHO recommendation on the use of Xpert as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having MDR-TB or HIV-associated TB," the authors concluded. Future studies should include those that evaluate the results of the test in children, as those data are starting to accumulate, and result of the test in different settings, such as TB screening centers and antiretroviral clinics, they added.

The review "provides high quality evidence that reinforces WHO’s endorsement of this test," Dr. Karin Weyer, the coordinator of Diagnostics and Drug Resistance Laboratories at WHO, said in a written statement. "Recent price reductions have greatly facilitated roll-out of this technology," with 1.4 million test cartridges and the instruments needed to perform the test to be distributed in 21 countries with a high TB burden, she added.

In the United States, TB has been declining, since a peak in 1992, with 10,528 TB cases reported in 2011, almost a 6% drop from the number of reports in 2010, according to the Centers for Disease Control and Prevention. In 2009, the last year mortality data are available, there were 529 TB deaths, a 10% drop from 2008, when there were 590 deaths.

The editorial base of the Cochrane Infectious Diseases Group (CIDG), which provided part of the funding for the review, is funded by the U.K. Department for International Development "for the benefit of developing countries." One study author disclosed having conducted studies and published on the Xpert test in a project with FIND, Cepheid, and academic partners. Others reported having no relevant financial conflicts.

e.mechcatie@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

©BananaStock/thinkstockphotos.com

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

fpnews@elsevier.com

The short-lived, worldwide epidemic of severe acute respiratory syndrome that began its streak across the globe 10 years ago, starting in February 2003, has been echoed over the past 8 months by what is so far a much more limited number of cases of a new, mysterious respiratory virus closely related to the SARS pathogen.

Mostly known so far as the "novel coronavirus" (NCoV), the new agent is very similar to the severe acute respiratory syndrome (SARS)-associated coronavirus, and by late February the new virus had been identified in 13 patients worldwide – in Saudi Arabia, Jordan, the United Kingdom, and Qatar – causing seven deaths and severe illness in five of the other six patients.

Since the World Health Organization (WHO) and other epidemiology groups first became aware of the NCoV last September, and as the number of identified cases has inched up, researchers have scrambled to gather information about the novel virus and heighten surveillance for new cases. SARS left a legacy of just over 8,000 probable cases in 29 countries, including 29 probable U.S. cases, with an overall fatality rate of 10%. After bursting on the scene in early 2003, SARS quickly flamed out, with the last handful of clinical cases ever seen identified in China in early 2004.

"It’s likely we will see more" of the NCoV. "We’ll need to cast a wide net since we now know there are a dozen cases and different clinical presentations," Dr. Larry Madoff said at the International Meeting on Emerging Diseases and Surveillance. Although almost every patient with confirmed NCoV infection has had severe illness, one U.K. patient who acquired the infection from another household member had a mild, flulike illness. The milder case "calls into question the [WHO] established case definition for this illness," said Dr. Madoff, director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston and chairman of the meeting’s program committee.

In the days after Dr. Madoff made that assessment at the meeting, the WHO on Feb. 21 reported the 13th case, a patient in Saudi Arabia first hospitalized in late January who died in mid-February.

An effort to track down the origin of the NCoV led to the area surrounding the Saudi Arabian city of Bisha, home of the first identified Saudi case. Suspecting a bat origin for the virus because the SARS-associated virus had been identified as a bat virus (although initial human transmission came via a civet), and because the human isolates of the NCoV could infect several bat-cell lines in the lab, U.S. epidemiologist Jonathan Epstein, D.V.M., led a team that surveyed bats from the Bisha area last fall to see if they could find coronaviruses similar to NCoV. Researchers previously reported finding NCoV-like viruses in bats from other locations that are related to the bats that live in the Bisha area, Dr. Epstein said at the meeting.*

"Everywhere you look in bats there seem to be one or two new coronaviruses, but most bat coronaviruses are not SARS-like. The novel coronavirus is the second bat coronavirus in addition to the SARS virus to cause a human infection," said Dr. Epstein, vice president for conservation medicine at EcoHealth Alliance, an environmental medical research organization based in New York.

"Based on published evidence, there is close relatedness between the novel coronavirus and the SARS virus, but SARS uses a receptor that is deep in the respiratory tract. The novel virus uses a different receptor. It’s not clear whether the novel virus can infect mucosa or the upper respiratory tract, but if it could it might be more transmissible," Dr. Epstein said in an interview.

A report from a team of Swiss researchers published on Feb. 19 (subsequent to Dr. Epstein’s comments) reported that the NCoV (which the Swiss researchers call human coronavirus [HCoV]-EMC) grew very efficiently in vitro on human bronchial epithelial cells, and that interferon treatment cut replication of the virus in these cells (mBio 2013;4:e00611-2).

IMNG Medical Media/Mitchel L. Zoler

The episodes of human infection by the NCoV so far that seem to be geographically disparate also have a precedent with SARS.

The pattern of cases "suggests that the source of the infection is common or widespread," Dr. Epstein said. "It’s a challenge to identify common environmental features in the case histories of the infected patients. But with SARS there were multiple spill-over events in different regions of southeast China" when the SARS virus moved from civets into people.

"There clearly are many unknowns about the epidemiology" of the NCoV, Dr. Marjorie R. Pollack, a consultant medical epidemiologist based in New York, wrote in a recent comment on the new coronavirus (ProMed Mail, 2013;Archive Number: 20130221.1554109). "Genetic studies on this NCoV place it related to coronaviruses found in bats. But how did the jump from bats to humans occur? Is there an intermediate host animal?"

According to recent guidance from the WHO, member states should "continue their surveillance for severe acute respiratory infections and to carefully review any unusual patterns. Testing for the NCoV should be considered in patients with unexplained pneumonias or in patients with unexplained severe, progressive or complicated respiratory illness not responding to treatment, particularly in persons traveling from or resident in areas of the world known to be affected."

Dr. Madoff, Dr. Epstein, and Dr. Pollack had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

*Correction, 3/1/2013: In an earlier version of this story, the findings regarding the Saudi Arabian bats sampled by Dr. Jonathan Epstein and his associates were misstated. Dr. Epstein and his colleagues led a team that surveyed bats from the Bisha area last fall. They have not yet reported their findings.

The short-lived, worldwide epidemic of severe acute respiratory syndrome that began its streak across the globe 10 years ago, starting in February 2003, has been echoed over the past 8 months by what is so far a much more limited number of cases of a new, mysterious respiratory virus closely related to the SARS pathogen.

Mostly known so far as the "novel coronavirus" (NCoV), the new agent is very similar to the severe acute respiratory syndrome (SARS)-associated coronavirus, and by late February the new virus had been identified in 13 patients worldwide – in Saudi Arabia, Jordan, the United Kingdom, and Qatar – causing seven deaths and severe illness in five of the other six patients.

Since the World Health Organization (WHO) and other epidemiology groups first became aware of the NCoV last September, and as the number of identified cases has inched up, researchers have scrambled to gather information about the novel virus and heighten surveillance for new cases. SARS left a legacy of just over 8,000 probable cases in 29 countries, including 29 probable U.S. cases, with an overall fatality rate of 10%. After bursting on the scene in early 2003, SARS quickly flamed out, with the last handful of clinical cases ever seen identified in China in early 2004.

"It’s likely we will see more" of the NCoV. "We’ll need to cast a wide net since we now know there are a dozen cases and different clinical presentations," Dr. Larry Madoff said at the International Meeting on Emerging Diseases and Surveillance. Although almost every patient with confirmed NCoV infection has had severe illness, one U.K. patient who acquired the infection from another household member had a mild, flulike illness. The milder case "calls into question the [WHO] established case definition for this illness," said Dr. Madoff, director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston and chairman of the meeting’s program committee.

In the days after Dr. Madoff made that assessment at the meeting, the WHO on Feb. 21 reported the 13th case, a patient in Saudi Arabia first hospitalized in late January who died in mid-February.

An effort to track down the origin of the NCoV led to the area surrounding the Saudi Arabian city of Bisha, home of the first identified Saudi case. Suspecting a bat origin for the virus because the SARS-associated virus had been identified as a bat virus (although initial human transmission came via a civet), and because the human isolates of the NCoV could infect several bat-cell lines in the lab, U.S. epidemiologist Jonathan Epstein, D.V.M., led a team that surveyed bats from the Bisha area last fall to see if they could find coronaviruses similar to NCoV. Researchers previously reported finding NCoV-like viruses in bats from other locations that are related to the bats that live in the Bisha area, Dr. Epstein said at the meeting.*

"Everywhere you look in bats there seem to be one or two new coronaviruses, but most bat coronaviruses are not SARS-like. The novel coronavirus is the second bat coronavirus in addition to the SARS virus to cause a human infection," said Dr. Epstein, vice president for conservation medicine at EcoHealth Alliance, an environmental medical research organization based in New York.

"Based on published evidence, there is close relatedness between the novel coronavirus and the SARS virus, but SARS uses a receptor that is deep in the respiratory tract. The novel virus uses a different receptor. It’s not clear whether the novel virus can infect mucosa or the upper respiratory tract, but if it could it might be more transmissible," Dr. Epstein said in an interview.

A report from a team of Swiss researchers published on Feb. 19 (subsequent to Dr. Epstein’s comments) reported that the NCoV (which the Swiss researchers call human coronavirus [HCoV]-EMC) grew very efficiently in vitro on human bronchial epithelial cells, and that interferon treatment cut replication of the virus in these cells (mBio 2013;4:e00611-2).

IMNG Medical Media/Mitchel L. Zoler

The episodes of human infection by the NCoV so far that seem to be geographically disparate also have a precedent with SARS.

The pattern of cases "suggests that the source of the infection is common or widespread," Dr. Epstein said. "It’s a challenge to identify common environmental features in the case histories of the infected patients. But with SARS there were multiple spill-over events in different regions of southeast China" when the SARS virus moved from civets into people.

"There clearly are many unknowns about the epidemiology" of the NCoV, Dr. Marjorie R. Pollack, a consultant medical epidemiologist based in New York, wrote in a recent comment on the new coronavirus (ProMed Mail, 2013;Archive Number: 20130221.1554109). "Genetic studies on this NCoV place it related to coronaviruses found in bats. But how did the jump from bats to humans occur? Is there an intermediate host animal?"

According to recent guidance from the WHO, member states should "continue their surveillance for severe acute respiratory infections and to carefully review any unusual patterns. Testing for the NCoV should be considered in patients with unexplained pneumonias or in patients with unexplained severe, progressive or complicated respiratory illness not responding to treatment, particularly in persons traveling from or resident in areas of the world known to be affected."

Dr. Madoff, Dr. Epstein, and Dr. Pollack had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

*Correction, 3/1/2013: In an earlier version of this story, the findings regarding the Saudi Arabian bats sampled by Dr. Jonathan Epstein and his associates were misstated. Dr. Epstein and his colleagues led a team that surveyed bats from the Bisha area last fall. They have not yet reported their findings.

The short-lived, worldwide epidemic of severe acute respiratory syndrome that began its streak across the globe 10 years ago, starting in February 2003, has been echoed over the past 8 months by what is so far a much more limited number of cases of a new, mysterious respiratory virus closely related to the SARS pathogen.

Mostly known so far as the "novel coronavirus" (NCoV), the new agent is very similar to the severe acute respiratory syndrome (SARS)-associated coronavirus, and by late February the new virus had been identified in 13 patients worldwide – in Saudi Arabia, Jordan, the United Kingdom, and Qatar – causing seven deaths and severe illness in five of the other six patients.

Since the World Health Organization (WHO) and other epidemiology groups first became aware of the NCoV last September, and as the number of identified cases has inched up, researchers have scrambled to gather information about the novel virus and heighten surveillance for new cases. SARS left a legacy of just over 8,000 probable cases in 29 countries, including 29 probable U.S. cases, with an overall fatality rate of 10%. After bursting on the scene in early 2003, SARS quickly flamed out, with the last handful of clinical cases ever seen identified in China in early 2004.

"It’s likely we will see more" of the NCoV. "We’ll need to cast a wide net since we now know there are a dozen cases and different clinical presentations," Dr. Larry Madoff said at the International Meeting on Emerging Diseases and Surveillance. Although almost every patient with confirmed NCoV infection has had severe illness, one U.K. patient who acquired the infection from another household member had a mild, flulike illness. The milder case "calls into question the [WHO] established case definition for this illness," said Dr. Madoff, director of epidemiology and immunization at the Massachusetts Department of Public Health in Boston and chairman of the meeting’s program committee.

In the days after Dr. Madoff made that assessment at the meeting, the WHO on Feb. 21 reported the 13th case, a patient in Saudi Arabia first hospitalized in late January who died in mid-February.

An effort to track down the origin of the NCoV led to the area surrounding the Saudi Arabian city of Bisha, home of the first identified Saudi case. Suspecting a bat origin for the virus because the SARS-associated virus had been identified as a bat virus (although initial human transmission came via a civet), and because the human isolates of the NCoV could infect several bat-cell lines in the lab, U.S. epidemiologist Jonathan Epstein, D.V.M., led a team that surveyed bats from the Bisha area last fall to see if they could find coronaviruses similar to NCoV. Researchers previously reported finding NCoV-like viruses in bats from other locations that are related to the bats that live in the Bisha area, Dr. Epstein said at the meeting.*

"Everywhere you look in bats there seem to be one or two new coronaviruses, but most bat coronaviruses are not SARS-like. The novel coronavirus is the second bat coronavirus in addition to the SARS virus to cause a human infection," said Dr. Epstein, vice president for conservation medicine at EcoHealth Alliance, an environmental medical research organization based in New York.

"Based on published evidence, there is close relatedness between the novel coronavirus and the SARS virus, but SARS uses a receptor that is deep in the respiratory tract. The novel virus uses a different receptor. It’s not clear whether the novel virus can infect mucosa or the upper respiratory tract, but if it could it might be more transmissible," Dr. Epstein said in an interview.

A report from a team of Swiss researchers published on Feb. 19 (subsequent to Dr. Epstein’s comments) reported that the NCoV (which the Swiss researchers call human coronavirus [HCoV]-EMC) grew very efficiently in vitro on human bronchial epithelial cells, and that interferon treatment cut replication of the virus in these cells (mBio 2013;4:e00611-2).

IMNG Medical Media/Mitchel L. Zoler

The episodes of human infection by the NCoV so far that seem to be geographically disparate also have a precedent with SARS.

The pattern of cases "suggests that the source of the infection is common or widespread," Dr. Epstein said. "It’s a challenge to identify common environmental features in the case histories of the infected patients. But with SARS there were multiple spill-over events in different regions of southeast China" when the SARS virus moved from civets into people.

"There clearly are many unknowns about the epidemiology" of the NCoV, Dr. Marjorie R. Pollack, a consultant medical epidemiologist based in New York, wrote in a recent comment on the new coronavirus (ProMed Mail, 2013;Archive Number: 20130221.1554109). "Genetic studies on this NCoV place it related to coronaviruses found in bats. But how did the jump from bats to humans occur? Is there an intermediate host animal?"

According to recent guidance from the WHO, member states should "continue their surveillance for severe acute respiratory infections and to carefully review any unusual patterns. Testing for the NCoV should be considered in patients with unexplained pneumonias or in patients with unexplained severe, progressive or complicated respiratory illness not responding to treatment, particularly in persons traveling from or resident in areas of the world known to be affected."

Dr. Madoff, Dr. Epstein, and Dr. Pollack had no disclosures.

m.zoler@elsevier.com

On Twitter @mitchelzoler

*Correction, 3/1/2013: In an earlier version of this story, the findings regarding the Saudi Arabian bats sampled by Dr. Jonathan Epstein and his associates were misstated. Dr. Epstein and his colleagues led a team that surveyed bats from the Bisha area last fall. They have not yet reported their findings.