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International Journal of Molecular... Feb 2021Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms... (Review)
Review
Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma's complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the genes were associated with childhood-onset asthma, interleukin (IL)33 and SNPs were associated with atopic asthma, and the gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.
Topics: Animals; Asthma; Epigenomics; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Immunity, Innate
PubMed: 33673725
DOI: 10.3390/ijms22052412 -
Allergology International : Official... Oct 2021Clinically and pathologically, the patients with hyper-IgE syndrome present similar skin manifestations to common atopic dermatitis. The original hyper-IgE syndrome is... (Review)
Review
Clinically and pathologically, the patients with hyper-IgE syndrome present similar skin manifestations to common atopic dermatitis. The original hyper-IgE syndrome is characterized by diminished inflammatory response, in combination with Staphylococcus aureus skin abscess and pneumonia followed by pneumatocele formation. These immunological manifestations are frequently associated with skeletal and connective tissue abnormalities. We previously identified that major causal variants of the hyper-IgE syndrome are dominant negative variants in the STAT3. In addition to the identification of new causative variants for the disorders similar to the original hyper-IgE syndrome, causative variants for new types of hyper-IgE syndrome centered only on atopy, high serum IgE levels, and susceptibility to infection, but not associated with diminished inflammatory response, pneumatocele formation, and connective tissue manifestations, have been identified. Recent discovery identified a novel zinc finger protein that regulates STAT3 transcription. Investigation of IL6ST variants disclosed that IL6ST/IL6R cytokine receptor plays a crucial role for the signal transduction upstream of STAT3 in the pathogenesis of the original hyper-IgE syndrome. Even if the same IL6ST variants are used for the signal transduction of IL-6 family cytokines, the signaling defect is more severe in IL-6/IL-11 and milder in LIF. The fact that the non-immune manifestations of the gain-of-function mutations of TGFBR1 and TGFBR2 are similar to the those of dominant negative mutations of STAT3 provide a clue to elucidate molecular mechanisms of non-immune manifestations of hyper-IgE syndrome. Research on this hereditary atopic syndrome is being actively conducted to elucidate the molecular mechanisms and to develop new therapeutic approaches.
Topics: Animals; CARD Signaling Adaptor Proteins; Guanylate Cyclase; Humans; Immunoglobulin E; Job Syndrome; Receptors, Cytokine; STAT3 Transcription Factor; Serine Peptidase Inhibitor Kazal-Type 5; TYK2 Kinase; Transcription Factors
PubMed: 34419355
DOI: 10.1016/j.alit.2021.07.007 -
The Journal of Allergy and Clinical... May 2023Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because... (Review)
Review
Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD.
Topics: Humans; Dermatitis, Atopic; Comorbidity; Asthma; Food Hypersensitivity; Rhinitis
PubMed: 36621338
DOI: 10.1016/j.jaci.2022.12.002 -
Current Allergy and Asthma Reports Apr 2023This review focuses on immunologic findings, relationships among immunologic findings and associated conditions of autoimmunity and atopy, and management of immunologic... (Review)
Review
PURPOSE OF REVIEW
This review focuses on immunologic findings, relationships among immunologic findings and associated conditions of autoimmunity and atopy, and management of immunologic disease in chromosome 22q11.2 deletion syndrome (22q11.2DS, historically known as DiGeorge syndrome).
RECENT FINDINGS
The implementation of assessment of T cell receptor excision circles (TRECs) in newborn screening has led to increased detection of 22q11.2 deletion syndrome. While not yet applied in clinical practice, cell-free DNA screening for 22q11.2DS also has the potential to improve early detection, which may benefit prompt evaluation and management. Multiple studies have further elucidated phenotypic features and potential biomarkers associated with immunologic outcomes, including the development of autoimmune disease and atopy. The clinical presentation of 22q11.2DS is highly variable particularly with respect to immunologic manifestations. Time to recovery of immune system abnormalities is not well-defined in current literature. An understanding of the underlying causes of immunologic changes found in 22q11.2DS, and the progression and evolution of immunologic changes over the lifespan have expanded over time and with improved survival. An included case highlights the variability of presentation and potential severity of T cell lymphopenia in partial DiGeorge syndrome and demonstrates successful spontaneous immune reconstitution in partial DiGeorge syndrome despite initial severe T cell lymphopenia.
Topics: Infant, Newborn; Humans; DiGeorge Syndrome; Chromosome Deletion; Neonatal Screening; Lymphopenia; Chromosomes
PubMed: 36897497
DOI: 10.1007/s11882-023-01071-4 -
The European Respiratory Journal Sep 2022In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is...
RATIONALE
In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.
OBJECTIVES
To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.
METHODS
In the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28.
MEASUREMENTS AND MAIN RESULTS
Based on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: "atopy-only", "eosinophils-only", "T2-high" (eosinophilia + atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood.
CONCLUSIONS
Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age.
Topics: Allergens; Asthma; Biomarkers; CD28 Antigens; Eosinophilia; Eosinophils; Humans; Immunoglobulin E; Interleukin-13; Interleukin-5; Lipopolysaccharides; Longevity; Phenotype
PubMed: 35210326
DOI: 10.1183/13993003.02288-2021 -
Pediatric Research Jul 2021Asthma is the most common chronic pediatric lung disease that has traditionally been defined as a syndrome of airway inflammation characterized by clinical symptoms of... (Review)
Review
Asthma is the most common chronic pediatric lung disease that has traditionally been defined as a syndrome of airway inflammation characterized by clinical symptoms of cough and wheeze. Highlighting the complex and heterogeneous nature of asthma, this review summarizes recent advances in asthma classification that are based on pathobiology, and thereby directly addresses limitations of existent definitions of asthma. By reviewing and contrasting clinical and mechanistic features of adult and childhood asthma, the review summarizes key biomarkers that distinguish childhood asthma subtypes. While atopy and its severity are important features of childhood asthma, there is evidence to support the existence of a childhood asthma endotype distinct from the atopic endotype. Although biomarkers of non-atopic asthma are an area of future research, we summarize a clinical approach that includes existing measures of airway-specific and systemic measures of atopy, co-existing morbidities, and disease severity and control, in the definition of childhood asthma, to empower health care providers to better characterize asthma disease burden in children. Identification of biomarkers of non-atopic asthma and the contribution of genetics and epigenetics to pediatric asthma burden remains a research need, which can potentially allow delivery of precision medicine to pediatric asthma. IMPACT: This review highlights asthma as a complex and heterogeneous disease and discusses recent advances in the understanding of the pathobiology of asthma to demonstrate the need for a more nuanced definitions of asthma. We review current knowledge of asthma phenotypes and endotypes and put forth an approach to endotyping asthma that may be useful for defining asthma for clinical care as well as for future research studies in the realm of personalized medicine for asthma.
Topics: Asthma; Biomarkers; Child; Humans; Inflammation; Phenotype; Respiratory Sounds
PubMed: 33173175
DOI: 10.1038/s41390-020-01231-6 -
Indian Journal of Ophthalmology Feb 2021Keratoconus is an ectatic corneal disease characterized by progressive stromal thinning, irregular astigmatism, and defective vision. It can be unilateral or bilateral... (Review)
Review
Keratoconus is an ectatic corneal disease characterized by progressive stromal thinning, irregular astigmatism, and defective vision. It can be unilateral or bilateral with asymmetric presentation. It starts at puberty and either progresses rapidly to an advanced stage of the disease or stops in case of delayed onset and slow progression. Pediatric keratoconus is more aggressive than in adults and the management protocols differ because of various rationales such as accelerated progression, advanced stage of disease at the time of diagnosis and co-morbidities. It poses a burden to the society as it affects the quality of life, social, and educational development in children. Hence early diagnosis, recognition of progression, and timely intervention with collagen crosslinking is imperative to arrest the worsening. Association with systemic syndromes and ocular comorbidities can be of concern in pediatric keratoconus. Severe ocular allergy when associated hastens progress and complicates timely intervention of crosslinking treatment and compliance to contact lens wear. Keratoplasty in pediatric keratoconus has good outcomes but can encounter frequent suture-related concerns. This article discusses the epidemiology, etiopathogenesis, clinical challenges, and current perspectives of management of pediatric keratoconus.
Topics: Adult; Astigmatism; Child; Collagen; Cornea; Corneal Topography; Corneal Transplantation; Humans; Keratoconus; Quality of Life
PubMed: 33463562
DOI: 10.4103/ijo.IJO_1263_20 -
Nutrients Feb 2023The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a... (Review)
Review
The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants. , DSM 17938, (BC50), Bb12, (CECT5716), and GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.
Topics: Infant, Newborn; Female; Child; Humans; Infant; Infant Formula; Probiotics; Breast Feeding; Milk, Human; Oligosaccharides
PubMed: 36904230
DOI: 10.3390/nu15051231 -
Deutsches Arzteblatt International Apr 2024According to self-reported frequencies, every fifth or sixth dwelling in Germany is affected by dampness and/or mold. This carries a potential risk to health. (Review)
Review
BACKGROUND
According to self-reported frequencies, every fifth or sixth dwelling in Germany is affected by dampness and/or mold. This carries a potential risk to health.
METHODS
This review is based on pertinent publications retrieved by a selective literature search and inquiry in the GENESIS database, on the AWMF guideline on the medical clinical diagnosis of indoor mold exposure, as updated in 2023, and on the relevant contents of other current guidelines. Based on this research, we present an algorithm for the evaluation of health problems that may be due to mold in indoor environments.
RESULTS
A rational diagnostic work-up begins with history-taking and physical examination, with attention to risk factors-above all, immune compromise and atopy. If there is evidence of atopy, targeted allergy diagnostics should be performed, consisting of a skin prick test and/or measurement of specific IgE antibodies, supplemented whenever indicated by provocative testing and cellular test systems. If the patient's immune response is compromised, the immediate cessation of mold exposure has absolute priority. Any suspected invasive fungal infection should be evaluated with radiological, microbiological, serological, and immunological testing. Indoor measurements of mold fungi, microbial volatile organic compounds (MVOC), and/or mycotoxins are generally not indicated as part of the medical evaluation; nor are blood or urine tests for particular mold components or metabolites.
CONCLUSION
Mold in indoor environments should be dealt with by rapid exposure elimination for patients at risk, the rational diagnostic evaluation of any symptoms and signs of disease, and patient education about the possibilities and limitations of diagnostic testing and the generally limited utility of measurements in the affected interior spaces.
Topics: Humans; Air Pollution, Indoor; Fungi; Germany; Mycoses
PubMed: 38381662
DOI: 10.3238/arztebl.m2024.0018