Interactions between genes and environmental factors in asthma and atopy: new developments

Asthma and associated phenotypes are complex traits most probably caused by an interaction of multiple disease susceptibility genes and environmental factors. Major achievements have occurred in identifying chromosomal regions and polymorphisms in candidate genes linked to or associated with asthma, atopic dermatitis, IgE levels and response to asthma therapy. The aims of this review are to explain the methodology of genetic studies of multifactorial diseases, to summarize chromosomal regions and polymorphisms in candidate genes linked to or associated with asthma and associated traits, to list genetic alterations that may alter response to asthma therapy, and to outline genetic factors that may render individuals more susceptible to asthma and atopy due to environmental changes

Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient's blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available

Allergen immunotherapy for allergic asthma: protocol for a systematic review

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma. Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. Discussion: The findings from this review will be used to inform the development of recommendations for EAACI’s Guidelines on AIT

La eficiencia del Plan Local de Seguridad Ciudadana 2019 del distrito El Porvenir para el cumplimiento del derecho fundamental a la tranquilidad de sus habitantes

La presente investigación tuvo como objetivo analizar el nivel de eficiencia del Plan Local de Seguridad Ciudadana 2019 del distrito de El Porvenir para el cumplimiento del derecho fundamental a la tranquilidad de sus habitantes. Para ello se utilizó un enfoque mixto (cuantitativo- cualitativo), transeccional con un alcance descriptivo y con un diseño no experimental, empleándose para la recolección de datos la recopilación de documentos, cuestionarios y entrevistas; la muestra seleccionada fue de tipo no probabilística por conveniencia y estuvo compuesta por 80 habitantes del distrito de El Porvenir y por 3 funcionarios públicos de la Municipalidad de El Porvenir, lográndose concluir de acuerdo con los resultados obtenidos de los cuestionarios medidos con la escala de Likert que el nivel de eficiencia del Plan Local de Seguridad Ciudadana 2019 del distrito de El Porvenir para dar cumplimiento al derecho fundamental de los habitantes es bajo; es decir, se aceptó la hipótesis general de la investigación

Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta‐analysis

Background and objectives: Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide. Methods: We performed a systematic search in PUBMED and EMBASE for population-based studies of cross-sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta-analysis, we used a random effects model. Results: Eighteen studies were included in the systematic evaluation and 11 in the meta-analysis including data from over 86 000 000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I-2) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%-CI 0.5-2.9) than those from Europe (0.5%, 0.2-1.0) and Northern American (0.1%, 0.1-0.1). Women were slightly more affected than men, whereas in children < 15 years we did not find a sex-specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time. Conclusions: On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex-specific population-based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors

Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

An Alu Element–Associated Hypermethylation Variant of the POMC Gene Is Associated with Childhood Obesity

The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron2–exon3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon3 methylation variant seems to result from an Alu element–triggered default state of methylation boundary definition. Exon3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity

A EUFOREA comment on a lost comorbidity of asthma

Abstract “Epidemiology of comorbidities and their association with asthma control” (Tomisa, G., Horváth, A., Sánta, B. et al. Epidemiology of comorbidities and their association with asthma control. Allergy Asthma Clin Immunol 17, 95 (2021). https://doi.org/10.1186/s13223-021-00598-3 ) is an interesting paper reflecting data collection from more than 12,000 asthmatic patients in Hungary regarding their condition and associated comorbidities. We found it valuable that the paper provides an overview of asthma comorbidities not usually considered in similar reports. Nevertheless, we believe that chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP or CRSsNP) should have been listed due to its high incidence and prevalence, its association with asthma which is also endorsed in both GINA and EPOS, as well as in several peer-reviewed scientific papers, and to reflect the role of this comorbidity in poor control and a most severe presentation of asthma for the patient. Consequently, several targeted therapies (especially monoclonal antibodies) used for several years in severe forms of asthma are now indicated also for the effective treatment of nasal polyps

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts

Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear.; We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE).; Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort.; The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk.; LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function