Background Gut microbiota may play a role in the natural history of cow's milk allergy. Objective We sought to examine the association between early-life gut microbiota and the resolution of cow's ...milk allergy. Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43; ANOVA P = .034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy.
ICON: Food allergy Burks, A. Wesley, MD; Tang, Mimi, MBBS, PhD; Sicherer, Scott, MD ...
Journal of allergy and clinical immunology,
04/2012, Letnik:
129, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the ...world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community.
Objectives This study sought to evaluate the long-term outcomes after transcatheter aortic valve implantation (TAVI) in the Multicenter Canadian Experience study, with special focus on the causes and ...predictors of late mortality and valve durability. Background Very few data exist on the long-term outcomes associated with TAVI. Methods This was a multicenter study including 339 patients considered to be nonoperable or at very high surgical risk (mean age: 81 ± 8 years; Society of Thoracic Surgeons score: 9.8 ± 6.4%) who underwent TAVI with a balloon-expandable Edwards valve (transfemoral: 48%, transapical: 52%). Follow-up was available in 99% of the patients, and serial echocardiographic exams were evaluated in a central echocardiography core laboratory. Results At a mean follow-up of 42 ± 15 months 188 patients (55.5%) had died. The causes of late death (152 patients) were noncardiac (59.2%), cardiac (23.0%), and unknown (17.8%). The predictors of late mortality were chronic obstructive pulmonary disease (hazard ratio HR: 2.18, 95% confidence interval CI: 1.53 to 3.11), chronic kidney disease (HR: 1.08 for each decrease of 10 ml/min in estimated glomerular filtration rate, 95% CI: 1.01 to 1.19), chronic atrial fibrillation (HR: 1.44, 95% CI: 1.02 to 2.03), and frailty (HR: 1.52, 95% CI: 1.07 to 2.17). A mild nonclinically significant decrease in valve area occurred at 2-year follow-up (p < 0.01), but no further reduction in valve area was observed up to 4-year follow-up. No changes in residual aortic regurgitation and no cases of structural valve failure were observed during the follow-up period. Conclusions Approximately one-half of the patients who underwent TAVI because of a high or prohibitive surgical risk profile had died at a mean follow-up of 3.5 years. Late mortality was due to noncardiac comorbidities in more than one-half of patients. No clinically significant deterioration in valve function was observed throughout the follow-up period.
Background Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment. ...Objective We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy. Methods In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed. Results At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants ( P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children ( P = 0.03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions ( P = .003). Increases in peanut-specific IgG4 levels and IgG4 /IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific TH 2 cytokines. Conclusions Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.
The Natural History of Food Allergy Savage, Jessica; Sicherer, Scott; Wood, Robert
The journal of allergy and clinical immunology in practice (Cambridge, MA),
03/2016, Letnik:
4, Številka:
2
Journal Article
Recenzirano
On a population level, it is well recognized that some IgE-mediated childhood food allergies, such as milk and egg allergies, are more likely to resolve than others, such as peanut and tree nuts ...allergies. Unfortunately, some studies suggest that resolution rates may have slowed compared with impressions from past decades. The clinician can apply the knowledge of the epidemiology of these allergies to describe likely patient outcomes, and direct management in a general manner. However, the ability to evaluate and predict the natural course of specific food allergies for individual patients is essential to inform personalized patient care. Data are accumulating to assist in identifying whether a child's allergy has likely resolved, informing the timing of oral food challenges or subsequent testing. Exciting recent studies are increasingly identifying early prognostic markers as well. Emerging food allergy therapies carry risks and costs. Identifying which egg-allergic patient has likely persistent allergy, and which patient with peanut allergy may experience natural resolution, is becoming an important goal to identify the best candidates for these therapies. Although more work needs to be done to identify reliable predictive markers and validate them, there is already much known about the natural course of food allergies that can be applied by the clinician to improve patient care.
In 2007, higher maternal vitamin D intake during pregnancy was shown to be associated with a lower risk of wheezing illnesses by age 3 and 5 years.2 Two subsequent studies examining 25-hydroxyvitamin ...D (25OHD) in cord blood found lower levels of cord blood 25(OH)D to be related to allergic sensitization3 and wheeze,4 but not asthma.3,4 Of 10 observational studies, half of which assessed vitamin D status by estimating dietary intake using questionnaires and half of which measured 25(OH)D in maternal serum or cord blood, 5 found a significantly reduced risk of asthma or atopy among children of mothers with higher vitamin D status during pregnancy, 3 found increased asthma or atopy risk in this same population, and the remaining 2 studies found no relationship.5 In current analyses, we used an objective measure of vitamin D status--the concentration of plasma 25(OH)D in umbilical cord blood--in 2 US birth cohorts with widely divergent populations to examine the relationship of vitamin D status at birth with various atopic and asthma-related outcomes in children after 5 to 6 years of follow-up. Because 25(OH)D concentrations can be highly variable, it is possible that cord blood concentrations, while reflecting vitamin D status at the end of pregnancy, may not fully reflect vitamin D exposure of the infant during critical time windows in pregnancy and development.
Food allergy is a common condition for which the only currently approved treatments are avoidance of the allergenic food and administration of emergency medications on accidental exposure. Over the ...past 10 years, significant advances have been made in the field of food immunotherapy, including oral immunotherapy, sublingual immunotherapy, and, more recently, epicutaneous immunotherapy. Each of these approaches are intended to induce some level of desensitization with chronic or repeated exposure to the allergenic food protein, although the risks and potential benefits of each treatment differ significantly. Although new data are emerging at a rapid pace and progress has been substantial, a number of important issues need to be addressed before introduction of these therapies into clinical practice. Furthermore, it is entirely possible that advances in this field will render these current approaches obsolete over the next 20 to 30 years as new and better therapies are developed.
Although there is concern that food allergy reactions may negatively affect the natural history of food allergy, the impact of reactions on food-specific IgE (sIgE) levels or skin prick test (SPT) ...wheal size is unknown.
To measure the effects of allergic reactions on SPT wheal size and sIgE concentrations to milk, egg, and peanut.
Participants included 512 infants with likely milk or egg allergy enrolled in a multicenter observational study. Changes in sIgE level and SPT wheal size to milk, egg, and peanut were measured before and after oral food challenge (OFC) or accidental exposure for 377 participants.
The median age of the cohort at the time of analysis was 8.5 years (67% males). There were no statistically significant changes in sIgE level or SPT wheal size after positive OFC to milk, egg, or peanut (n = 20-27 for each food). Change in sIgE level and SPT wheal size was measured after 446 and 453 accidental exposure reactions, respectively. The median change in sIgE level was a decrease of 0.33 kU(A)/L (P < .01) after milk and 0.34 kU(A)/L (P < .01) after egg reactions, but no other statistically significant changes in sIgE level or SPT wheal size were observed for milk, egg, or peanut. When we limited the analysis to only those participants who had diagnostic testing done within 6 months of an accidental exposure reaction, we found that peanut SPT wheal size increased by 1.75 mm (P < .01), but a significant increase was not noted when all participants with testing done within 12 months were considered.
The results suggest that reactions from OFCs and accidental exposure are not associated with increases in sensitization among children allergic to milk, egg, or peanut.
Background Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly ...diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. Objective We sought to test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. Methods We enrolled 40 children aged 9 to 36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/d in a double-blinded fashion. The primary end point, sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving 4 prespecified criteria, or after 3 maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared with 154 matched standard-care controls. Results Of 40 consented subjects, 3 (7.5%) did not qualify. Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 85%; 3000 mg, 12 of 17 71%, P = .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). Allergic side effects during E-OIT were common but all were mild to moderate. Conclusions At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.
Background Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these ...approaches are limited. Objective This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT. Methods In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged. Results Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT ( P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. Conclusion OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.
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