This survey study examines changes in pediatric clinicians’ knowledge of eczema identification and the 2017 Addendum Guidelines for the Prevention of Peanut Allergy after an educational intervention.
For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic ...reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.
We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.
Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8–44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61–80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 who received placebo met the primary outcome of desensitisation (risk difference RD 69%, 95% CI 59–79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755–5005) for peanut oral immunotherapy versus 5 mg (0–105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13–30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10–28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0–2755) for peanut oral immunotherapy and 0 mg (0–55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.
In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.
National Institute of Allergy and Infectious Disease, Immune Tolerance Network.
Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy ...has been shown to improve symptoms for at least 2 years following discontinuation of treatment.
To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.
A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.
Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).
Total nasal symptom scores (TNSS; range; 0 best to 12 worst) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.
Among 106 randomized participants (mean age, 33.5 years; 34 women 32.1%), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; P = .75).
Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.
clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.
Staphylococcus aureus has been implicated in the pathophysiology of eczema, allergic rhinitis, asthma, and food allergy. S aureus is a marker of more severe eczema, which is a risk factor for food ...sensitization/allergy. Therefore it might be that the association between S aureus and food allergy in eczematous patients is related to eczema severity.
We sought to investigate the association of S aureus colonization with specific IgE (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity. We additionally determined the association of S aureus colonization with eczema severity and persistence.
In Learning Early About Peanut Allergy (LEAP) study participants eczema severity was assessed, and skin/nasal swabs were cultured for S aureus. Sensitization was identified by measuring sIgE levels. Peanut allergy was primarily determined by means of oral food challenge, and persistent egg allergy was primarily determined by using skin prick tests.
Skin S aureus colonization was significantly associated with eczema severity across the LEAP study, whereas at 12 and 60 months of age, it was related to subsequent eczema deterioration. Skin S aureus colonization at any time point was associated with increased levels of hen's egg white and peanut sIgE independent of eczema severity. Participants with S aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity. All but one of the 9 LEAP study consumers with peanut allergy (9/312) were colonized at least once with S aureus.
S aureus, independent of eczema severity, is associated with food sensitization and allergy and can impair tolerance to foods. This could be an important consideration in future interventions aimed at inducing and maintaining tolerance to food allergens in eczematous infants.
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Background
Introducing peanut products early can prevent peanut allergy (PA). The “Addendum guidelines for the prevention of PA in the United States” (PPA guidelines) recommend early introduction of ...peanut products to low and moderate risk infants and evaluation prior to starting peanut products for infants at high risk for PA (those with severe eczema and/or egg allergy). Rapid adoption of guidelines could aid in lowering the prevalence of PA. The Intervention to Reduce Early (Peanut) Allergy in Children (iREACH) trial was designed to promote PPA guideline adherence by pediatric clinicians.
Methods
A two‐arm, cluster‐randomized, controlled clinical trial was designed to measure the effectiveness of an intervention that included clinician education and accompanying clinical decision support tools integrated in electronic health records (EHR) versus standard care. Randomization was at the practice level (n = 30). Primary aims evaluated over an 18‐month trial period assess adherence to the PPA guidelines using EHR documentation at 4‐ and 6‐month well‐child care visits aided by natural language processing. A secondary aim will evaluate the effectiveness in decreasing the incidence of PA by age 2.5 years using EHR documentation and caregiver surveys. The unit of observation for evaluations are individual children with clustering at the practice level.
Conclusion
Application of this intervention has the potential to inform the development of strategies to speed implementation of PPA guidelines.
Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. ...The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific.
We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization.
Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement.
A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption.
Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.
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Background Early introduction of peanut is an effective strategy to prevent peanut allergy in high-risk infants; however, feasibility and effects on growth and nutritional intake are unknown. ...Objective We sought to evaluate the feasibility of introducing peanut in infancy and explore effects on growth and nutritional intake up to age 60 months. Methods In the Learning Early About Peanut Allergy trial, 640 atopic infants aged 4 to 11 months were randomly assigned to consume (6 g peanut protein per week) or avoid peanut until age 60 months. Peanut consumption and early feeding practices were assessed by questionnaire. Dietary intake was evaluated with prospective food diaries. Anthropometric measurements were taken at all study visits. Results Peanut was successfully introduced and consumed until 60 months, with median peanut protein intake of 7.5 g/wk (interquartile range, 6.0-9.0 g/wk) in the consumption group compared with 0 g in the avoidance group. Introduction of peanut in breast-feeding infants did not affect the duration of breast-feeding. There were no differences in anthropometric measurements or energy intakes between groups at any visits. Regular peanut consumption led to differences in dietary intakes. Consumers had higher intakes of fat and avoiders had higher carbohydrate intakes; differences were greatest at the upper quartiles of peanut consumption. Protein intakes remained consistent between groups. Conclusions Introduction of peanut proved feasible in infants at high risk of peanut allergy and did not affect the duration of breast-feeding nor impact negatively on growth or nutrition. Energy balance was achieved in both groups through variations in intakes from fat and carbohydrate while protein homeostasis was maintained.
Objectives. The present study sought to determine whether myocardial contractile abnormalities accompany the development of chest pain in patients with normal coronary angiograms.
Background. The ...mechanism of chest pain in patients with angina despite a normal coronary arteriogram is controversial. Although previous studies postulated the existence of coronary microvascular dysfunction, others failed to find evidence of myocardial ischemia, and recent studies have demonstrated abnormal cardiac sensitivity in these patients that can lead to chest pain on a nonischemic basis.
Methods. Seventy patients (26 men and 44 women, mean age 49 ± 10 years) with angina-like chest pain and angiographically normal coronary arteries underwent exercise treadmill testing, radionuclide angiography at rest and during exercise, thallium stress testing and transesophageal dobutamine stress echocardiography. The results of exercise treadmill testing and stress echocardiography were compared with those obtained in 26 normal control subjects (19 men and 7 women, mean age 56 ± 7 years).
Results. Abnormalities consistent with myocardial ischemia were noted in 31% of the patients during exercise treadmill testing, in 16% during exercise radionuclide angiography and in 18% during thallium stress testing. The findings of the radionuclide studies were not concordant with one another and were not related to the presence of repolarization changes during exercise testing. During infusion of dobutamine, chest pain developed in 59 patients (84%) and in none of the control subjects (p < 0.0001); repolarization changes occurred in 22 patients (34%) and in 2 control subjects (8%) (p < 0.04). None of the patients or the control subjects developed regional wall motion abnormalities with dobutamine. The quantitative myocardial contractile response to dobutamine was similar in patients and control subjects, with an 80% power to detect a 25% difference in systolic wall thickening at the maximal dose of dobutamine.
Conclusions. There was no agreement in the results of noninvasive tests in our patients. Despite the frequent provocation of chest pain and electrocardiographic abnormalities with dobutamine, the patients demonstrated a quantitatively normal myocardial contractile response without development of wall motion abnormalities. These observations strongly suggest that myocardial ischemia is not the cause of chest pain in patients with a normal coronary arteriogram.
(J Am Coll Cardiol 1997;29:293–301)
Both thallium scintigraphy and dobutamine echocardiography have been used to assess myocardial viability. However, thallium uptake and the inotropic response to dobutamine are expressions of ...different cellular phenomena. The present study was undertaken to investigate the relation between the two methods in patients with chronic coronary artery disease and left ventricular dysfunction to derive insights into the mechanisms related to myocyte viability.
Thirty patients (28 men and 2 women; age, 59 +/- 10 years) with chronic coronary artery disease and impaired left ventricular systolic function at rest (mean ejection fraction, 32 +/- 9%) were included in the study. Patients underwent transesophageal echocardiography during incremental doses of dobutamine from 2.5 to a maximum of 40 micrograms.kg-1.min-1 and single photon emission computed tomographic thallium scintigraphy using a stress-redistribution-reinjection protocol. The left ventricle was divided into 16 segments for analysis of echocardiographic and thallium images. Segmental myocardial contractile function was graded as normal, hypokinesis, akinesis, or dyskinesis at each incremental dose of dobutamine. Thallium uptake in each myocardial segment was graded on a 5-point scale from 0 (absent) to 2 (normal) for each of the stress, redistribution, and reinjection images. A segment was considered viable if the assigned thallium score was 1 or higher (normal uptake or only mild to moderate defect) in any of the stress, redistribution, or reinjection images. Among 472 myocardial segments available for analysis, 311 had resting wall motion abnormalities, of which 56% (173/311) showed contractile improvement with dobutamine (usually first observed at < or = 10 micrograms.kg-1.min-1) and 84% (262/311) were considered viable by thallium scintigraphy (P < .0001). Of the 262 segments considered viable by thallium, 167 (64%) had a contractile improvement with dobutamine; in contrast, only 6 of the 49 segments (12%) considered nonviable by thallium had a positive dobutamine response (P < .0001). Furthermore, a positive inotropic response to dobutamine was significantly related to the magnitude of thallium uptake: the proportion of segments with a positive dobutamine response rose with increasing magnitude of thallium uptake (P < .001). The disagreement between the two tests was related primarily to segments considered viable by thallium that did not show contractile improvement with dobutamine.
These findings demonstrate the existence of a relation between thallium uptake and the inotropic response to dobutamine in patients with chronic coronary artery disease and left ventricular dysfunction. However, the proportion of segments showing a positive response to dobutamine is significantly lower than those with thallium uptake, suggesting that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake.
Assessment of left ventricular (LV) volumes and mass is a critical element in the evaluation of patients with cardiovascular disease. However, most non-invasive methods used for the quantitative ...measurements of LV volume and mass have important intrinsic limitations. Real-time 3-dimensional echocardiography (RT3D echo) is a new technique capable of acquiring volumetric images without cardiac or respiratory gating. The purpose of this study was to develop and validate a system for rapid LV volume and mass measurements with the use of RT3D echo images. To this end, in 11 explanted sheep hearts, the left ventricle was instrumented with a latex balloon and filled with known volumes of saline solution. Two independent observers made volume calculations from images acquired with RT3D echo. In addition, 21 open-chest sheep were imaged with RT3D echo for LV mass calculation. Anatomic LV mass was determined after removing the heart. A strong correlation was observed between the actual LV volumes and those calculated from the RT3D echo images (r = 0.99; y = 1.31 + 0.98x; standard error of the estimate = 2.2 mL). An analysis of intraobserver and interobserver variabilities revealed high indexes of agreement. A strong correlation was observed between actual LV mass and that calculated from RT3D echo images (r = 0.94; y = 14.4 + 0.89x; standard error of the estimate = 8.5 gm). Thus RT3D echo images allow rapid and accurate measurements of LV volume and mass. This technique may expand the use of cardiac ultrasonography for the quantitative assessment of heart disease.
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