Medical Journal Review
May 2023
WAO Reviews – Editors' Choice
The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.
Timing of allergenic food introduction and risk of immunoglobulin E-mediated food allergy: A systematic review and meta-analysis
Scarpone R, Kimkool P, Ierodiakonou D et al
JAMA Pediatrics 2023;177(5):489-497
https://doi.org/10.1001/jamapediatrics.2023.0142
Earlier egg and peanut introduction probably reduce the risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction. Thus, the objective of this study was to investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy. To do so, the authors performed a systematic review and meta-analysis, searching for articles from database inception to December 29, 2022, including search terms of: infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes. Screening was conducted independently by multiple authors, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISM) guideline, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess certainty of evidence. The primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods.
Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13,794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I 2 = 49%). Absolute risk difference for a population with 5% incidence of food allergy was −26 cases (95% CI, −34 to −13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I 2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I 2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I 2 = 21%). Evidence for timing of introduction of cow’s milk and risk of cow’s milk allergy was very low certainty.
Overall, the results indicated through this systematic review and meta-analysis that earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy, but a high rate of withdrawal from the intervention was seen.
Severe asthmatic responses: The impact of TSLP
Theofani E, Tsitsopoulou A, Morianos I, Semitekolou M
International Journal of Molecular Sciences 2023;24(8):7581
https://doi.org/10.3390/ijms24087581
It is well known that patients with severe asthma (SA) represent a group of asthmatics that are poorly responsive to medium-to-high doses of inhaled corticosteroids and additional controllers, thus leading in some cases to life-threatening disease exacerbations. To elaborate on SA heterogeneity, the concept of asthma endotypes has been developed, with the latter being characterized as T2-high or low, depending on the type of inflammation implicated in disease pathogenesis. As SA patients exhibit curtailed responses to standard-of-care treatment, biologic therapies are prescribed as adjunctive treatments. To date, several biologics that target specific downstream effector molecules involved in disease pathophysiology have displayed superior efficacy only in patients with T2-high, eosinophilic inflammation. This is not surprising, as until recently, all of the biologic therapies available targeted T2 mediators, including IgE, IL5, and IL4/13. In the case of the T2 low subset of SA, upstream mediators of the inflammatory cascade could constitute an attractive therapeutic approach for difficult-to-treat asthma. One such appealing therapeutic target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine with critical functions in allergic diseases, including asthma. This review explores the numerous studies in both humans and mice that provided major insights pertinent to the role of TSLP in the initiation and propagation of the asthmatic responses.
Associations between fetal or infancy pet exposure and food allergies: The Japan Environment and Children’s Study (JECS)
Okabe H, Hashimoto K, Yamada M et al
PLoS One 2023;18(3):e0282725
https://doi.org/10.1371/journal.pone.0282725
The hygiene hypothesis suggests that pet exposure is effective in preventing allergic disease, and some studies have reported the beneficial effects of dog exposure during fetal development or early infancy on food allergy. However, the effects of exposure to pets other than dogs on the impact of food allergies remains unaddressed. This study aimed to explore the effect of exposure to various species of pets on the risk of food allergies. To do so, Okabe and colleagues obtained information on pet exposure and food allergy from the Japan Environment and Children’s Study (JECS), a nationwide, prospective birth cohort study that included 97,413 mothers and their children and examined the associations between exposure to various species of pets during fetal development or early infancy and the incidence risk of food allergies. They then applied logistic regression analysis for each pet species, causative food, and timing of exposure.
They found that exposure to dogs or cats during fetal development or early infancy was estimated to reduce the incidence risk of food allergies until the age of 3 years. Dog exposure was estimated to reduce the incidence risk of egg, milk, and nut allergies, and cat exposure was estimated to reduce the incidence risk of egg, wheat, and soybean allergies. However, hamster exposure was estimated to increase the incidence risk of nut allergy.
The authors conclude that the association between pet exposure and food allergies might differ depending on the pet species and causative food. Continued dog and cat exposure from fetal development to infancy was estimated to reduce the incidence risk of food allergies.
EAACI Molecular Allergology User’s Guide 2.0
Dramburg S, Hilger C, Santos AF et al
Pediatric Allergy and Immunology 2023; 34(28):e13854
https://doi.org/10.1111/pai.13854
Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The field of molecular allergology is moving quickly and after 6 years, a new EAACI Taskforce was established to provide an updated document of the “EAACI Molecular Allergology User's Guide”. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergens available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure. This publication should serve as a great resource for the practicing allergist.
Development and validation of a respiratory-responsive vocal biomarker-based tool for generalizable detection of respiratory impairment: Independent case-control studies in multiple respiratory conditions including asthma, chronic obstructive pulmonary disease, and COVID-19
Kaur S, Larsen E, Harper J, Purandare B et al
Journal of Medical Internet Research 2023;25:e44410 (14 Apr)
https://doi.org/10.2196/44410
The use of vocal biomarker–based machine learning approaches have shown promising results in the detection of various health conditions, including respiratory diseases, such as asthma. In this study by Kaur and colleagues, the authors aimed to determine whether a respiratory-responsive vocal biomarker (RRVB) model platform initially trained on an asthma and healthy volunteer (HV) data set could differentiate patients with active COVID-19 infection from asymptomatic HVs by assessing its sensitivity, specificity, and odds ratio (OR). The authors relied upon a logistic regression model using a weighted sum of voice acoustic features was previously trained and validated on a data set of approximately 1700 patients with a confirmed asthma diagnosis and a similar number of healthy controls. The same model has shown generalizability to patients with chronic obstructive pulmonary disease, interstitial lung disease, and cough. In this study, 497 participants (female: n=268, 53.9%; <65 years old: n=467, 94%; Marathi speakers: n=253, 50.9%; English speakers: n=223, 44.9%; Spanish speakers: n=25, 5%) were enrolled across 4 clinical sites in the United States and India and provided voice samples and symptom reports on their personal smartphones. The participants included patients who are symptomatic COVID-19 positive and negative as well as asymptomatic HVs. The RRVB model performance was assessed by comparing it with the clinical diagnosis of COVID-19 confirmed by reverse transcriptase–polymerase chain reaction.
The ability of the RRVB model to differentiate patients with respiratory conditions from healthy controls was previously demonstrated on validation data in asthma, chronic obstructive pulmonary disease, interstitial lung disease, and cough, with ORs of 4.3, 9.1, 3.1, and 3.9, respectively. The same RRVB model in this study in COVID-19 performed with a sensitivity of 73.2%, specificity of 62.9%, and OR of 4.64 (P<.001). Patients who experienced respiratory symptoms were detected more frequently than those who did not experience respiratory symptoms and completely asymptomatic patients (sensitivity: 78.4% vs 67.4% vs 68%, respectively) than those who did not experience respiratory symptoms and completely asymptomatic patients (sensitivity: 78.4% vs 67.4% vs 68%, respectively).
The authors conclude that the generalizability of this model for detecting respiratory symptoms across different linguistic and geographic contexts suggests a potential path for the development and validation of voice-based tools for broader disease surveillance and monitoring applications in the future.
