Childhood atopic disorders in relation to placental changes-A systematic review and meta-analysis.

Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.

Accidental allergic reactions to immediate-type food allergens in Japanese children: A single-center study.

BACKGROUND: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. METHODS: This study included children with immediate-type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low-dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. RESULTS: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3-8.6) years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annualized AAR rate was 0.130 (0.109-0.153) in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p < .001 and p = .036). CONCLUSION: In this single-center study in Japan, the annualized AAR rate was relatively low during the COVID-19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low-dose reactivity, children would require careful AAR risk management.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.

Does having siblings really protect against childhood atopic diseases? A total population and within-family analysis.

The association between having older siblings and decreased risk for atopic symptoms is well-established. This has been interpreted as evidence for the microbiota hypothesis, i.e. that increased early-childhood microbial exposure caused by siblings protects from immune hypersensitivities. However, possible confounders of the association have received little attention. We used register data on Finnish cohorts born in 1995-2004 (N = 559,077) to assess medication purchases for atopic diseases: antihistamines, eczema medication, asthma medication and Epinephrine. We modelled the probability of atopic medication purchases at ages 0-15 by birth order controlling for important observed confounders and all unobserved genetic and environmental characteristics shared by siblings in a within-family fixed effects model. We further studied medication purchases among first-borns according to the age difference with younger siblings to assess whether having younger siblings in early childhood is beneficial. Having older siblings was associated with a lower probability of atopic medication purchases. Compared to first-borns, the probability was 10-20% lower among second-borns, 20-40% lower among third-borns, and 30-70% lower among subsequent children, depending on medication type. Confounding accounted for up to 75% of these differences, particularly for asthma and eczema medication, but significant differences by birth order remained across all medication types. Among first-borns, a smaller age difference with younger siblings was related to a lower likelihood of atopic medication use. Our results, based on designs that account for unobserved confounding, show that exposure to siblings in early childhood, protects from atopic diseases, and thus strongly support the microbiota hypothesis.

Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

The mycobiome in atopic diseases: Inducers and triggers.

Atopic diseases are characterized by type 2 inflammation, with high levels of allergen-specific TH2 cell immune responses and elevated production of IgE. These common disorders have increased in incidence around the world, which is partly explained by detrimental disturbances to the early-life intestinal microbiome. Although most studies have focused exclusively on bacterial members of the microbiome, intestinal fungi have started to be recognized for their impact on host immune development and atopy pathogenesis. From this perspective, we review recent findings demonstrating the strong interactions between members of the mycobiome and the host immune system early in life, leading to immune tolerance during eubiosis or inducing sensitization and overt TH2 cell responses during dysbiosis. Current evidence places intestinal fungi as central players in the development of allergic diseases and potential targets for atopy prevention and treatments.

Zinc finger protein 33B demonstrates sex interaction with atopy-related markers in childhood asthma.

BACKGROUND: Sex differences related to immune responses can influence atopic manifestations in childhood asthma. While genome-wide association studies have investigated a sex-specific genetic architecture of the immune response, gene-by-sex interactions have not been extensively analysed for atopy-related markers including allergy skin tests, IgE and eosinophils in asthmatic children. METHODS: We performed a genome-wide gene-by-sex interaction analysis for atopy-related markers using whole-genome sequencing data based on 889 trios from the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) and 284 trios from the Childhood Asthma Management Program (CAMP). We also tested the findings in UK Biobank participants with self-reported childhood asthma. Furthermore, downstream analyses in GACRS integrated gene expression to disentangle observed associations. RESULTS: Single nucleotide polymorphism (SNP) rs1255383 at 10q11.21 demonstrated a genome-wide significant gene-by-sex interaction (pinteraction=9.08×10-10) for atopy (positive skin test) with opposite direction of effects between females and males. In the UK Biobank participants with a history of childhood asthma, the signal was consistently observed with the same sex-specific effect directions for high eosinophil count (pinteraction=0.0058). Gene expression of ZNF33B (zinc finger protein 33B), located at 10q11.21, was moderately associated with atopy in girls, but not in boys. CONCLUSIONS: We report SNPs in/near a zinc finger gene as novel sex-differential loci for atopy-related markers with opposite effect directions in females and males. A potential role for ZNF33B should be studied further as an important driver of sex-divergent features of atopy in childhood asthma.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

Immediate Hypersensitivity to Chlorhexidine: Experience from an Allergy Center in China.

BACKGROUND: Chlorhexidine generally has a good safety profile. However, allergic reactions are reported with increasing frequency. In China, it is rarely reported, and its characteristics are unknown. The purpose of this study was to summarize the experience of a Chinese allergy center with chlorhexidine allergy. METHODS: The authors retrospectively reviewed all patients who underwent chlorhexidine allergy testing in the Allergy Center of West China Hospital, Sichuan University (Chengdu, China), in the period February 2018 to May 2022 (n = 43 patients) and included the patients diagnosed with chlorhexidine allergy for analysis. RESULTS: Ten patients who were diagnosed by skin prick and serum-specific immunoglobulin E tests were included. They experienced a total of 30 allergic reactions to chlorhexidine (mean ± SD, 3.0 ± 1.3). Five patients experienced six allergic reactions (6 of 30, 20%) during general or local anesthesia, and they may have been exposed to chlorhexidine via different routes. Only one allergic reaction (1 of 30, 3%) was recorded with exposure via a mouthwash. The other 23 allergic reactions (23 of 30, 77%) were caused via a skin disinfectant; the route of exposure was IV cannulation in 22 allergic reactions (22 of 23, 96%) and broken skin in one allergic reaction (1 of 23, 4%). The symptoms included a quick onset and great severity. Two patients (2 of 10, 20%) had been accidentally re-exposed to chlorhexidine after diagnosis. CONCLUSIONS: This study conducted in China showed that the majority of reactions to chlorhexidine were attributed to skin disinfectants, and IV cannulation was the most common exposure route; in general, however, chlorhexidine allergy was easily overlooked. The potential allergenicity of chlorhexidine used for skin preparation before IV cannulation or should be considered in patients who develop allergic reactions perioperatively.

Clinical features and later prognosis of replicable early-life wheeze clusters from two birth cohorts 12 years apart.

BACKGROUND: Clustering techniques can define the heterogeneity of asthma and wheezing. Defining early-life wheezing clusters and associated asthma risk could potentially inform patient management strategies. Clustering models that yield replicable cluster groups will have greater validity and clinical utility. This study sought to identify early-life wheezing clusters that are translatable into clinical practice and assess their stability over time in two whole-population birth cohorts established a decade apart from the same geographical location. METHODS: Nonparametric K-means cluster analysis was performed separately on two birth cohorts from the Isle of Wight, UK; the Isle of Wight Birth Cohort (IOWBC) and Food Allergy and Intolerance Research Cohort (FAIR), using clinically defining variables in wheezing subjects in the first 3-4 years. Associations of resulting clusters with potential early-life risk factors and 10-year asthma outcomes were further assessed. RESULTS: Five clusters were identified in both cohorts: (1) infantile-onset-transient-non-atopic-wheeze, (2) infantile-onset-persistent-non-atopic-wheeze, (3) infantile-onset-atopic-wheeze, (4) early-childhood-onset-non-atopic-wheeze, and (5) early-childhood-onset-atopic-wheeze. Two atopic wheezing clusters (3 and 5) were associated with greatest early-life wheeze frequency, highest wheeze persistence, and asthma prevalence at 10 years. Cluster 1 was commonest but had lowest early-life wheeze frequency and asthma prevalence at 10 years. Cluster 2, characterized by limited atopy but recurrent infantile respiratory infections and ongoing early-life wheezing, had high 10-year asthma prevalence only in IOWBC. CONCLUSIONS: Early-life wheeze comprises several disease clusters (two more severe and three mild-moderate) with differing relationships to later childhood asthma, which can be replicated over time supporting their potential validity and clinical utility.

Impact of histamine-2 antagonist shortage on the incidence of hypersensitivity reactions to paclitaxel: a reconsideration of premedication protocols in France (PACLIREACT Study).

PURPOSE: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. METHODS: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. RESULTS: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). CONCLUSION: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A.

Atopy and allergy following solid organ transplantation: A 15-year experience.

AIM: There are increasing reports of atopy/allergy following solid organ transplantation, especially paediatric liver transplantation (LT) with minimal New Zealand (NZ) data. We describe the prevalence of transplant-acquired atopy and allergy (TAA) in NZ paediatric liver transplant recipients, compared to paediatric kidney and adult liver transplants. METHODS: TAA focussed health questionnaires were sent to patients selected from the NZ transplant registry (transplanted between January 2003 and December 2017). Demographic and clinical data were also obtained from electronic health records and follow-up phone calls. RESULTS: A total of 232 patients (62% male) participated (111 adult liver, 82 paediatric liver, 39 paediatric kidney transplant recipients). Tacrolimus was primary immunosuppression for all LT patients; with combined tacrolimus, mycophenolate and corticosteroids for kidney transplants. The number of patients who developed TAA was significantly higher (P < 0.001) in the paediatric LT group (36/82, 44%) compared to adult liver (12/111, 11%) and paediatric kidney transplants (4/39, 10%). Eczema was most common (73%), then IgE-mediated food allergy (FA, 33%), allergic rhinitis (19%) and asthma (17%). Six paediatric LT recipients developed eosinophilic oesophagitis (EoE). Egg was the most common allergen in the IgE-mediated FA group. TAAs were severe enough to warrant a switch from tacrolimus to another agent in seven paediatric LT patients. For paediatric LT patients, female gender and younger age at transplant were risk factors for developing TAA. CONCLUSIONS: TAA is common in paediatric liver transplant recipients, with female gender and younger age at transplant being risk factors identified. This highlights the need for detailed atopic and allergy history to be incorporated in all pre-transplant assessments.

Systematic review on skin adverse effects of important hazardous hair cosmetic ingredients with a focus on hairdressers.

BACKGROUND: The burden of occupational hand eczema in hairdressers is high, and (partly strong) allergens abound in the hair cosmetic products they use. OBJECTIVES: To systematically review published evidence concerning contact allergy to an indicative list of active ingredients of hair cosmetics, namely, p-phenylenediamine (PPD), toluene-2,5-diamine (PTD), persulfates, mostly ammonium persulfate (APS), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG), concerning the prevalence of sensitization, particularly in terms of a comparison (relative risk; RR) between hairdressers and non-hairdressers. METHODS: Following a PROSPERO-registered and published protocol, eligible literature published from 2000 to February 2021 was identified, yielding 322 publications, and extracted in standardized publication record forms, also considering risk of bias. RESULTS: Based on 141 publications, the contact allergy prevalence to PPD was 4.3% (95% CI: 3.8-4.9%) in consecutively patch tested patients. Other ingredients were mostly tested in an aimed fashion, yielding variable, and partly high contact allergy prevalences. Where possible, the RR was calculated, yielding an average increased sensitization risk in hairdressers of between 5.4 (PPD) and 3.4 (ATG). Additional evidence related to immediate-type hypersensitivity, experimental results, exposures, and information from case reports was qualitatively synthesized. CONCLUSIONS: An excess risk of contact allergy is clearly evident from the pooled published evidence from the last 20 years. This should prompt an improvement in working conditions and product safety.

Atopic children are more susceptible to viral respiratory infection at the age of 2-5 years old.

Background: The susceptibility of the atopic population to respiratory infections (RI) has not been fully elucidated. This susceptibility is attributed to the immune dysregulation that characterizes atopic diseases. Although, the exact mechanisms involved are not fully understood, there is evidence that shows that the maturation of innate immunity progresses differently in patients with atopy. Objective: The aim of the study was to evaluate the susceptibility to viral RIs (VRI) based on the number and duration of them in different age groups in subjects with atopy and subjects without atopy. Methods: Seventy-eight subjects (39 healthy and 39 with atopy) were included in the study. All the subjects were evaluated by a specialist and defined as being atopic if they had a clinical history and/or symptoms compatible with any allergic diseases and relevant sensitizations. Epidemiologic data were recorded based on a standardized questionnaire, which included recording habits, conditions, and living environment as well as the history of viral infections during the last year. Results: In our population, children with atopy were found to be more susceptible to viral RIs than children without atopy (p = 0.02), whereas there was no difference in susceptibility between healthy adults and adults with atopy (18-45 years old). More specifically, the atopic age group 2-5 years old showed the higher susceptibility to VRIs. Conclusion: This study provided evidence that children with atopy, especially at ages 2-5 years old, had more numerically and prolonged RIs than did the subjects without atopy. These clinical findings support the hypothesis of distracted maturation of innate immunity in subjects with atopy.

Prenatal antibiotic exposure, asthma, and the atopic march: A systematic review and meta-analysis.

Antibiotic use during pregnancy may increase the risk for asthma in children. We performed a meta-analysis assessing prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march. A systematic literature search protocol (PROSPERO-ID: CRD42020191940) was registered and searches were completed using Medline, Proquest, Embase, and the Cochrane central register of controlled trials. Screening for inclusion criteria: published in English, German, French, Dutch, or Arabic, intervention (use of any antibiotic at any time point during pregnancy), and disease (reporting atopic disease incidence in children with a primary outcome of asthma or wheeze), and exclusion criteria: reviews, preclinical data, and descriptive studies, yielded 27 studies. Study quality was assessed using the Newcastle-Ottawa Assessment Scale. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Our meta-analysis demonstrates that antibiotic use during pregnancy is associated with an increased relative risk (RR) of developing wheeze RR 1.51 (95% CI: 1.17-1.94) or asthma RR 1.28 (95% CI 1.22-1.34) during childhood. Assessment of the atopic march in association with asthma or wheeze revealed that antibiotic use during pregnancy also increases the risk for eczema/dermatitis RR 1.28 (95% CI: 1.06-1.53) and allergic rhinitis RR 1.13 (95% CI: 1.02-1.25). One study found an increase in food allergy RR 1.81 (95% CI: 1.11-2.95). Maternal antibiotic use during pregnancy is associated with an increased risk for wheeze or asthma development in children, as well as for diseases involved in the atopic march. There was high heterogeneity in the data, and the certainty of the evidence was determined to be low quality, highlighting the need for more high-quality studies on this topic. These results have importance for antibiotic stewardship throughout the prenatal period. This work was supported by the Deutsche Forschungsgemeinschaft and the Konrad Adenauer Foundation.

Concurrent allergy and helminthiasis in underprivileged urban South African adults previously residing in rural areas.

This study investigated whether prior exposure to helminths (Ascaris IgE, Ascaris eggs and Trichuris eggs) either in childhood or in adulthood, and residence in rural and resource-limited urban areas influence allergy outcomes (asthma, rhinitis, IgE atopy and food allergy) in a South African population. Participants historical and present allergies data were collected through questionnaires and clinical record files. Coproscopy and immunoassays (ImmunoCAPTM Phadiatop, total IgE and allergen-specific fx3 IgE immunoassays and Ascaris IgE radioallergosorbent [RAST] tests) were used for active helminthiasis and allergy screens respectively. Data were analysed using logistic regression analysis, and models were adjusted for age, gender and locality. High Ascaris IgE was significantly associated with asthma (adjusted odds ratio [aOR] = 2.20, p = .047), IgE atopy (aOR = 18.18, p < .0001) and food allergy (aOR = 14.47, p < .0001). Asthma was significantly less likely among participants with Ascaris eggs (aOR = 0.43, p = .048) and Trichuris eggs (aOR = 0.36, p = .024). The findings of co-occurrent helminthiasis and allergic disorders in a population that has resided both in rural and peri-urban informal settlements both oppose and agree with two main notions of the hygiene hypothesis that (i) individuals residing in rural settings with poor sanitation and geohelminth infection are less prone to allergy, and (ii) helminth infections protect against allergy respectively. Further research is warranted.

Early-life cytomegalovirus infection is associated with gut microbiota perturbations and increased risk of atopy.

BACKGROUND: The "old friends" hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the "old friends" hypothesized to help prevent allergic diseases. We sought to elucidate whether early-life CMV infection is associated with childhood atopy via perturbations of the gut microbiota. METHODS: Participants were recruited from a population-based birth cohort (CHILD study) and followed prospectively until age 5 years in four Canadian cities. A total of 928 participants provided stool microbiome data, urine for CMV testing, skin prick tests, and questionnaire-based detailed environmental exposures. Cytomegalovirus infection was assessed in the first year of life while the main outcome was defined by persistent sensitization to any allergen at ages 1, 3, and 5 years. RESULTS: Early CMV infection was associated with increased beta and decreased alpha diversity of the gut microbiota. Both changes in diversity measures and early CMV infection were associated with persistent allergic sensitization at age 5 years (aOR = 2.08; 95% CI: 1, 4.33). Mediation analysis demonstrated that perturbation of gut microbial composition explains 30% of the association. CONCLUSIONS: Early-life CMV infection is associated with an alteration in the intestinal microbiota, which mediates the effect of the infection on childhood atopy. This work indicates that preventing CMV infection would not put children at increased risk of developing atopy. Rather, a CMV vaccine, in addition to preventing CMV-associated morbidity and mortality, might reduce the risk of childhood allergic diseases.

Prevalence of eosinophilic, atopic, and overlap phenotypes among patients with severe asthma in Saudi Arabia: a cross-sectional study.

BACKGROUND: Eosinophilia is a significant factor in asthma severity; however, the prevalence of severe eosinophilic asthma in Saudi Arabia is largely unknown. We aimed to determine the prevalence of the eosinophilic (defined in this study as ≥ 300 cells/mm3 in blood), atopic (atopic phenotype 1, defined in this study as > 100 IU/mL total serum IgE; atopic phenotype 2, defined in this study as > 150 IU/mL), and overlap phenotypes among patients with severe asthma in Saudi Arabia. METHODS: A cross-sectional study was conducted in centers specialized in severe asthma management. Patients aged ≥ 12 years with severe asthma were enrolled. Study patients responded to the Global Initiative for Asthma 2018 assessment of asthma control questionnaire and provided study investigators with current information related to the study objectives. Additional medical record data and a blood sample for total serum IgE and complete blood count were collected. RESULTS: A total of 101 patients were enrolled; 83% were female and the mean (standard deviation) age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes. CONCLUSIONS: In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype. Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.

Inborn errors of immunity manifesting as atopic disorders.

Inborn errors of immunity are traditionally best known for enhancing susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in patients with inborn errors of immunity. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize that allergic diseases such as food allergy, atopic dermatitis, and allergic asthma are expressions of misdirected immunity, and in patients who present with severe, early-onset, or coexisting allergic conditions, these can be indications of an underlying PAD. Identifying monogenic allergic disease through next-generation sequencing can dramatically improve outcomes by allowing the use of precision-based therapy targeting the patient's underlying molecular defect. It is therefore imperative that clinicians recognize PADs to be able to provide informed therapeutic options and improve patient outcomes. Here, we summarize the clinical features commonly seen with each of the currently known PADs, identify clinical warning signs that warrant assessment for PADs, and lastly, discuss the benefits of timely diagnosis and management of these conditions.

Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years.

BACKGROUND: Early-life exposures to geohelminths may protect against development of wheeze/asthma and atopy. OBJECTIVE: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years. METHODS: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. RESULTS: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. CONCLUSIONS: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).