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The Journal of Pediatrics May 2021To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. (Clinical Trial)
Clinical Trial Comparative Study
OBJECTIVES
To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition.
STUDY DESIGN
In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula.
RESULTS
In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort.
CONCLUSIONS
The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.
Topics: Amino Acids; Asthma; Caseins; Child, Preschool; Conjunctivitis, Allergic; Dermatitis, Atopic; Female; Follow-Up Studies; Humans; Immune Tolerance; Incidence; Infant; Infant Formula; Lacticaseibacillus rhamnosus; Male; Milk Hypersensitivity; Oryza; Probiotics; Prospective Studies; Rhinitis, Allergic; Glycine max; Treatment Outcome; Whey
PubMed: 33524387
DOI: 10.1016/j.jpeds.2021.01.059 -
The Journal of Allergy and Clinical... Jun 2024Local allergic rhinitis (LAR) is defined by a clinical history suggestive of allergic rhinitis (AR), negativity of systemic IgE measurement and positive response to... (Review)
Review
Local allergic rhinitis (LAR) is defined by a clinical history suggestive of allergic rhinitis (AR), negativity of systemic IgE measurement and positive response to nasal allergen challenge (NAC). The term local respiratory allergy includes LAR, local allergic asthma (positive response in bronchial allergen challenge) and dual allergic rhinitis defined by the coexistence of AR and LAR. LAR worsens in severity and presence of comorbidities over time, and it is an independent entity from AR. Prevalence is higher in Mediterranean countries. LAR onset occurs during childhood in 36% of cases. Physiopathological features of LAR are: increased nasal eosinophilic inflammation, tryptase and eosinophil cationic protein, and presence of nasal specific IgE in secretions of 20-40% of subjects. A recent study demonstrated increase in sequential class switch recombination to IgE markers in mucosa of LAR with accumulation of IgE+ CD38+ plasmablasts. Moreover, there is increased expression in B cells of mucosal homing receptors CXCR3+ and CXCR4 in peripheral blood, with accumulation of Th9 and Th2 cells. NAC is the gold standard in the diagnosis of LAR. The measurement of specific IgE in nasal secretions basophil activation test or are still not suitable for diagnosis. There is ample evidence of the usefulness of allergen immunotherapy in the treatment in LAR after 4 DBPCRT in 152 patients. In conclusion, knowledge about LAR is continuously increasing, with detailed definition of physiopathological mechanisms and new phenotypes. More awareness of the disease should be promoted among different specialists, and NAC must be considered an essential diagnostic tool in any age group, including children.
Topics: Humans; Rhinitis, Allergic; Immunoglobulin E; Allergens; Desensitization, Immunologic; Nasal Provocation Tests; Child
PubMed: 38641133
DOI: 10.1016/j.jaip.2024.04.021 -
American Journal of Respiratory and... Feb 2024Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not...
Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV% predicted improvement of 3.2% (95% CI, 1.0-5.3; = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.
Topics: Adult; Humans; Rhinitis; Cohort Studies; Asthma; Comorbidity; Chronic Disease; Sinusitis; Biological Products; Rhinitis, Allergic; Nasal Polyps
PubMed: 38016003
DOI: 10.1164/rccm.202305-0808OC -
The Journal of Allergy and Clinical... Oct 2022Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action...
BACKGROUND
Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood.
OBJECTIVE
We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.
METHODS
We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response.
RESULTS
Antigen-stimulated culturing after SLIT led to clonal expansion of T2 and regulatory T cells, and most of these CD4 T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional T2 cells but increased the trans-type T2 cell population that expresses musculin (MSC), TGF-β, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type T2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment.
CONCLUSION
The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic T2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.
Topics: Allergens; Biomarkers; Cryptomeria; Humans; Immunologic Factors; Interleukin-2; Leukocytes, Mononuclear; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Sublingual Immunotherapy; Transforming Growth Factor beta
PubMed: 35863510
DOI: 10.1016/j.jaci.2022.06.024 -
Autoimmunity Reviews Jan 2022Allergic disorders target a young population, are increasing in both incidence and prevalence and are associated with significant disease burden. They result from the... (Review)
Review
Allergic disorders target a young population, are increasing in both incidence and prevalence and are associated with significant disease burden. They result from the complex interplay between (epi)genetic and environmental factors, resulting in a Th2 inflammatory process targeting the epithelium of the respiratory tract (allergic rhinitis and asthma), skin (atopic dermatitis), and gastrointestinal tract (food allergy). Although the exact pathogenic mechanisms remain elusive, an altered immune system response in the gut is increasingly recognized as a relevant step. Allergic and gastrointestinal autoimmune disorders share several epidemiological, pathogenic and risk factors and several treatment modalities. Here we revise the current literature and show that allergic disorders are highly prevalent in gastrointestinal autoimmune diseases, including celiac disease, inflammatory bowel disease, autoimmune pancreatitis, and autoimmune cholangiopathies. No data are available for some autoimmune diseases, such as autoimmune gastritis and autoimmune enteropathy. To ensure the comprehensive care of patients with autoimmune gastrointestinal disorders, along with disease-specific factors, the presence of allergic disorders should be evaluated and treated when present, possibly targeting shared molecular pathways. Future studies are needed to define the exact pathogenic mechanisms underpinning the association between allergic and autoimmune diseases of the gastrointestinal tract.
Topics: Autoimmune Diseases; Dermatitis, Atopic; Gastrointestinal Diseases; Humans; Rhinitis, Allergic
PubMed: 34560305
DOI: 10.1016/j.autrev.2021.102958 -
Expert Review of Clinical Pharmacology 2023Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic... (Review)
Review
INTRODUCTION
Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergen-specific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids.
AREAS COVERED
This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR.
EXPERT OPINION
The management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT.
Topics: Humans; Rhinitis, Allergic; Histamine Antagonists; Desensitization, Immunologic; Asthma; Adrenal Cortex Hormones; Allergens
PubMed: 37314373
DOI: 10.1080/17512433.2023.2225770 -
Pediatric Allergy and Immunology :... May 2021Rhinitis-and especially allergic rhinitis (AR)-remains the most frequent hypersensitivity condition, affecting up to a quarter of the population and impacting the... (Review)
Review
Rhinitis-and especially allergic rhinitis (AR)-remains the most frequent hypersensitivity condition, affecting up to a quarter of the population and impacting the quality of life of individual patients and the health economy. Data, especially with respect to underlying pathophysiologic mechanisms, mainly derive from studies on adults and are subsequently extrapolated to the pediatric population. Therapeutic algorithms for children with rhinitis are long based on the same principles as in adults. We explore and describe novel aspects of rhinitis, ranging from mechanisms to disease classification, phenotypes, diagnostic and monitoring tools, and the use of treatments, with a focus on the traits of pediatric age groups.
Topics: Child; Humans; Quality of Life; Rhinitis; Rhinitis, Allergic
PubMed: 33475171
DOI: 10.1111/pai.13454 -
Otolaryngologic Clinics of North America Apr 2024Allergic rhinitis (AR) is associated with increased sleep disturbances in adults and children. Pathogenesis is multifactorial, with nasal obstruction playing a large... (Review)
Review
Allergic rhinitis (AR) is associated with increased sleep disturbances in adults and children. Pathogenesis is multifactorial, with nasal obstruction playing a large role. Intranasal corticosteroids, antihistamines, leukotriene inhibitors, and allergen immunotherapy have been demonstrated to relieve self-reported symptoms of sleep impairment. Given the high prevalence of sleep impairment in AR, providers should consider evaluating any patient with AR for sleep disturbances and sleep-disordered breathing.
Topics: Child; Adult; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic; Sleep; Histamine Antagonists; Sleep Apnea Syndromes; Sleep Wake Disorders
PubMed: 37867109
DOI: 10.1016/j.otc.2023.09.003 -
PLoS Pathogens Sep 2023The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now... (Review)
Review
The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20-30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don't understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter.
Topics: Humans; Inflammation; Rhinitis, Allergic; Asthma; Eukaryota
PubMed: 37703276
DOI: 10.1371/journal.ppat.1011623 -
Cells Dec 2022Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to... (Review)
Review
Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to be normally involved in the progression of most non-neoplastic diseases, including brain injury, ocular diseases, chronic rhinosinusitis, allergic rhinitis, dental diseases, atopic dermatitis, scleroderma, eosinophilic esophagitis, asthma, cardiovascular diseases, lung diseases, liver diseases, chronic kidney diseases, inflammatory bowel disease, and osteoarthrosis. Periostin interacts with protein receptors and transduces signals primarily through the PI3K/Akt and FAK two channels as well as other pathways to elicit tissue remodeling, fibrosis, inflammation, wound healing, repair, angiogenesis, tissue regeneration, bone formation, barrier, and vascular calcification. This review comprehensively integrates the multiple roles of periostin and its variants in non-neoplastic diseases, proposes the utility of periostin as a biological biomarker, and provides potential drug-developing strategies for targeting periostin.
Topics: Humans; Asthma; Dermatitis, Atopic; Inflammation; Phosphatidylinositol 3-Kinases; Rhinitis, Allergic
PubMed: 36611844
DOI: 10.3390/cells12010050