Atopic Status Research Articles

Sensitization to Staphylococcus Enterotoxin: Relationship with Aspects of Disease Severity

Background/Objective: Sensitization to specific IgE Staphylococcus aureus enterotoxins (SEs) is associated with an increased risk for severe asthma development. Limited data exist regarding the association of seropositivity for specific IgE SEs and the different aspects of severe asthma. We aimed to determine whether the presence of SEs is associated with asthma-related parameters such as inflammatory cells in the airways, features of airway remodeling, and other variables relating to asthma assessment and severity. Methods: Fifty patients with severe asthma were recruited in the study. Demographics, comorbidities, asthma duration, and asthma medication were recorded by treating physicians. Specific IgE SE measurement, lung function, atopic status, asthma control test (ACT), sputum induction, bronchoscopy with BAL, and indices of airway remodeling were also assessed. Results: Twelve patients were positive to enterotoxin sensitization. Patients seropositive to specific IgE SEs significantly differed in regard to FEV1% pred and FEV1/FVC ratio compared to seronegative ones. Analyzing the inflammatory variables obtained from induced sputum, BAL, and endobronchial biopsies, the only significant difference was that of smooth muscle area (SMA), which was greater in specific IgE SE seropositive patients. The multivariate linear regression analysis showed two significant associations of specific IgE SE seropositivity. We found a negative with FEV1% pred with beta standardized coefficient 95%CI −0.054 (−0.083, −0.031), p < 0.001, and a positive with SMA with beta standardized coefficient 95%CI 0.054 (0.081, 0.037), p < 0.001. Conclusions: Seropositivity to specific IgE SEs in severe asthma is associated with more severe airflow limitation, obstruction, and upregulation in SMA, indicating a possible role in the remodeling process.

Impact of Atopic Status on Clinical Presentation and Treatment Response in Pediatric Patients With Eosinophilic Esophagitis

BackgroundNearly 80% of patients with eosinophilic esophagitis have co-existing atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy. ObjectivesTo characterize the presentation and response to therapy in atopic versus non-atopic pediatric patients with EoE MethodsA case-control study of EoE patients, ages 6 months to 18 years (between 2018-2021) was performed. Patients were eligible if they had allergy testing, assessment of atopic history, and at least one endoscopy following initiation of treatment. Patients were considered non-atopic if they had negative allergy testing and no history of significant atopy. Response to therapy was classified as complete (peak eos < 15/hpf), partial (≥ 15 eos/hpf but at least a 50% reduction in peak eos), or non-response. Results168 participants were enrolled. The majority were white (n=141, 84%), male (n=124, 74%), and non-Hispanic (n=158, 95%). Mean age at diagnosis was 9.4 years (SD: ± 4.8). 123 participants (73.2%) were atopic and 45 (26.8%) were non-atopic. There was no significant difference between atopic and non-atopic for most demographics or presenting symptoms. Non-atopic participants presented younger than atopic participants (8.14 vs. 9.8 years, p=0.046). Swallowed topical corticosteroids (STC) and food elimination diets (FED) were utilized at a similar rate. There were no differences in treatment response between atopic/non-atopic participants in regards to STC, FED, or STC+FED. ConclusionAtopic status does not significantly impact presentation or response to treatment in pediatric EoE, but a lack of atopy may be a risk for earlier onset of disease.

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.

Sociodemographic inequities in food allergy: Insights on food allergy from birth cohorts.

A large and growing corpus of epidemiologic studies suggests that the population-level burden of pediatric FA is not equitably distributed across major sociodemographic groups, including race, ethnicity, household income, parental educational attainment, and sex. As is the case for more extensively studied allergic disease states such as asthma and atopic dermatitis epidemiologic data suggest that FA may be more prevalent among certain populations experiencing lower socioeconomic status (SES), particularly those with specific racial and ethnic minority backgrounds living in highly urbanized regions. Emerging data also indicate that these patients may also experience more severe FA-related physical health, psychosocial, and economic outcomes relating to chronic disease management. However, many studies that have identified sociodemographic inequities in FA burden are limited by cross-sectional designs that are subject to numerous biases. Compared with cross-sectional study designs or cohorts established later in life, birth cohorts offer advantages relative to other study designs when investigators seek to understand causal relationships between exposures occurring during the prenatal or postnatal period and the atopic disease status of individuals later in life. Numerous birth cohorts have been established across recent decades, which include evaluation of food allergy-related outcomes, and a subset of these also have measured sociodemographic variables that, together, have the potential to shed light on the existence and possible etiology of sociodemographic inequities in food allergy. This manuscript reports the findings of a comprehensive survey of the current state of this birth cohort literature and draws insights into what is currently known, and what further information can potentially be gleaned from thoughtful examination and further follow-up of ongoing birth cohorts across the globe.

Evidence for 2 clusters among patients with noneosinophilic asthma

BackgroundAlthough asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. ObjectiveTo apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. MethodsOur cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). ResultsCluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. ConclusionNoneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.

Altered COVID-19 immunity in children with asthma by atopic status

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Safety of partial selective COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity and factors affecting safety

Aims: Partial selective COX-2 inhibitors, such as nimesulide, or meloxicam are tolerated by the majority of the patients with cross-reactive NSAID hypersensitivity. This study aimed to obtain more information about the safety of partial selective COX-2 inhibitors; nimesulide and meloxicam in non-immunologic type, cross-reactive NSAID hypersensitivity and to detect risk factors for intolerance to these drugs.&#x0D; Methods: This is a retrospective study of patients with suggestive of cross-reactive NSAID hypersensitivity who admitted to our clinic over a period of 10 years. Patients who had a reliable history of immediate type NSAIDs hypersensitivity with at least 2 chemically unrelated class and/or positive ASA provocation test and who underwent alternative drug provocation test with partial selective COX-2 inhibitors (nimesulide and/or meloxicam) were included to study. Patients’ demographics, comorbidities, atopy status, duration of NSAID hypersensitivity, total number of reactions, reaction grades, clinical phenotypes, pulmonary function test parameters and results of alternative drug provocation test results are recorded. Patients with and without reactions during alternative provocation tests with nimesulide and/or meloxicam were compared in terms of these data. &#x0D; Results: A total of 560 patients were included in the study, 378 (67.5%) of them were female. Allergic comorbidities were detected in 394 (72.6%) patients. Asthma, other drug allergies and nasal polyp were the most common comorbidities. Alternative drug provocation test positivity with nimesulide and/or meloxicam was detected in 50 of 560 (8.9%) patients. Provocation test positivity was 33/541 (6.1%) with nimesulide, 30/517 (5.8%) with meloxicam and 13/498 (2.3%) with both nimesulide and meloxicam. Duration of NSAID hypersensitivity was shorter and allergic comorbidities, asthma, nasal polyp and the coexistence of asthma and nasal polyp were more common in patients with a positive provocation test.&#x0D; Conclusion: The partial selective COX-2 inhibitors nimesulide and meloxicam are well tolerated alternatives in patients with cross-reactive NSAID hypersensitivity. Hypersensitivity to these drugs is significantly higher in patients with asthma and/or nasal polyp than other group of cross-reactive NSAID hypersensitive patients and also in patients with a shorter duration of NSAID hypersensitivity.

Screening asthmatics for atopic status using the ALergy EXplorer (ALEX2) macroarray

Background Screening asthma patients for atopy facilitates management. Since 2010, the core biomarker for screening asthma subjects for atopic status has been the qualitative Phadiatop. multi-aeroallergen screen. A more quantitative macroarray, the Allergy Explorer (ALEX2), shows promise as an alternative. Objective The study’s goal was to examine the pros and cons of the use of ALEX2 in the screening of asthma patients for atopic status. Methods We evaluated the atopic (IgE-sensitization) status in asthmatic Amish and Hutterite farm children using the ImmunoCAP and ALEX2 assays in Phadiatop equivocal and positive subjects. Results All 42 asthmatic children were analyzed by Phadiatop and total serum IgE. Of these, 22 had a negative Phadiatop (<0.1 kUa/L) and total IgE <100 kU/L which defined them as non-atopic and they were excluded from ALEX2 testing. Of six children with equivocal Phadiatops (0.1–0.2 kUa/L-Group 1) and three children with a negative Phadiatop but total IgE >100 kUa/L (group 3), 44% (n = 4) had detectable IgE antibody by ALEX2 to mite, tree pollen, and other allergens not detected by Phadiatop, but confirmed by allergen-specific ImmunoCAP testing. In 11 Phadiatop positive subjects (>0.2 kUa/L–group 2), all but one were positive by ALEX2. IgE antibody specific for mold and rabbit aeroallergens matched their agricultural and pet exposure history. Three children were positive for IgE antibody to allergens in the profilin, nsLTP, or PR-10 cross-reactive protein families. Conclusion Judicious use of ALEX2’s enhanced specificity data not provided by the Phadiatop can aid in the interpretation of sensitization patterns and planning management of atopic asthmatics, but sensitization relevance must be confirmed by the patient’s clinical history.

Identification of the major immune differences in severe asthmatic children according to their atopic dermatitis status

Severe asthma (SA) affects 2% to 5% of asthmatic children. Atopic dermatitis can affect up to 34% of children with SA (cwSA). Atopic dermatitis and asthma share common genetic and immunological features. However, not all children with SA suffer from AD, and it remains unclear whether the overall immune profiles of these children are similar. In this study, seventeen cwSA (9.8 [7.1–13.2] years; seven with and ten without AD) were enrolled. Bronchoalveolar lavage (BAL) and blood samples were collected from these patients. Seventy-three cytokines/chemokines and distinct immune T cell populations were evaluated in blood and BAL. We found that BAL and blood immune profiles of cwSA with and without AD were globally similar. However, specific differences were observed, namely lower frequency of Tc2, Th17 and IL-17-producing mucosal associated invariant T (MAIT-17) cells and higher CD8/CD4 ratio and IL-22 concentrations in BAL and of CCL19 concentrations in plasma from cwSA with AD. Further, in contrast with cwSA without AD, we found a positive correlation between a set of plasma cytokines and almost all cytokines in BAL in cwSA with AD. In conclusion, this study shows the major immune differences between cwSA with and without AD in BAL and blood suggesting that distinct endotypes may be implicated in the inflammatory responses observed in these pediatric patients.

The impact of intranasal corticosteroids in a prospective cohort of children with sleep disordered breathing

IntroductionSleep disordered breathing (SDB) is common in children and the most common reason for adenotonsillectomy. This large observational cohort study from a specialist outpatient clinic describes the impact of intranasal steroids (INS) on symptom improvement and the need for surgery. MethodObservational cohort study of 568 children assessing the impact of INS using the OSA-5 questionnaire with clinical and surgical outcome measures. ResultsThe mean OSA-5 score at first visit was 7.78. Symptoms were persistent for a median 9 months (range 2–72). 51% underwent a trial of INS with 56% reporting symptomatic improvement. The mean score decreased from 8.2 to 5.5 (p < 0.0001) in those prescribed INS. They had a significantly higher symptom load (p < 0.01), turbinate size (p < 0.005) and history of atopy (p < 0.01) than the non-trial group. The rate of surgery in the non-trial group was 56% compared with 38% in those who had INS (p < 0.001). With increasing symptom burden, the reported improvement with INS and comparative reduction in surgery increased. Baseline OSA-5 scores were predictive of rates of surgery. Atopic status or age did not influence response to INS. ConclusionThe mean score at first visit and the median duration of symptoms indicated significant persistent symptoms in this cohort. The use of INS improved symptoms of SDB in 56%. The need for surgery in the group that received INS was 38% compared with 56% in those not trialling INS, despite the non-trial group having significantly less symptoms and signs. Symptomatic improvement was not influenced by age or atopic status.

Sleep and allergic diseases among young Chinese adults from the Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) cohort

Background and objectiveSleep disruption has been shown to affect immune function and thus influence allergic disease manifestation. The specific effects of sleep on allergic diseases, however, are less well-established; hence, in a unique population of young Chinese adults, we investigated the association between sleep and allergic disease.MethodsYoung Chinese adults recruited from Singapore in the Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) were analyzed. We used the International Study of Asthma and Allergies in Childhood (ISAAC) protocol and a skin prick test to determine atopic dermatitis (AD), allergic rhinitis (AR), and asthma status. Information regarding total sleep time (TST) and sleep quality (SQ) was also obtained.ResultsOf 1558 participants with a mean age of 25.0 years (SD = 7.6), 61.4% were female, and the mean total sleep time (TST) was 6.8 h (SD = 1.1). The proportions of AD, AR, and asthma were 24.5% (393/1542), 36.4% (987/1551), and 14.7% (227/1547), respectively. 59.8% (235/393) of AD cases suffered from AD-related sleep disturbances, 37.1% (209/564) of AR cases suffered from AR-related sleep disturbances, and 25.1% (57/227) of asthma cases suffered from asthma-related sleep disturbances. Only asthma cases showed a significantly lower mean TST than those without asthma (p = 0.015). Longer TST was significantly associated with lower odds of AR (OR = 0.905, 95% CI = 0.820–0.999) and asthma (OR = 0.852, 95% CI = 0.746–0.972). Linear regression analyses showed that lower TST was significantly associated with asthma (β = − 0.18, SE = 0.076, p-value = 0.017), and AR when adjusted for AR-related sleep disturbances (β = − 0.157, SE = 0.065, p-value = 0.016). Only sleep disturbances due to AR were significantly associated with a poorer SQ (OR = 1.962, 95% CI = 1.245–3.089).ConclusionsWe found that sleep quality, but not sleep duration was significantly poorer among AD cases, although the exact direction of influence could not be determined. In consideration of the literature coupled with our findings, we posit that TST influences allergic rhinitis rather than vice versa. Finally, the association between TST and asthma is likely mediated by asthma-related sleep disturbances, since mean TST was significantly lower among those with nighttime asthma symptoms. Future studies could consider using objective sleep measurements coupled with differential expression analysis to investigate the pathophysiology of sleep and allergic diseases.

P831 Acute infusion reactions due to different biologic agents in a large cohort of patients with Inflammatory Bowel Disease

Abstract Background The therapeutic armamentarium for inflammatory bowel disease (IBD) includes several biological agents: infliximab (IFX), adalimumab (ADA), vedolizumab (VED) and ustekinumab (UST). Persistence in therapy with these drugs is not satisfactory, not only due to the loss of clinical response over time but also due to adverse events. Acute infusion reactions (AIRs) occur during or within 24 hours of the infusion. The intensity of AIRs ranges from mild (flushing, dizziness, headache, itching, rash) to severe (anaphylactic). The primary aim of this study was to compare the prevalence rates of AIRs due to the different biological agents in a large cohort of patients with IBD and to assess risk factors for AIRs. Methods All reports of AIRs occurring from January 2021 to October 2023 in IBD patients treated with different biological agents (IFX, ADA, VED and UST) in a tertiary IBD center were retrospectively reviewed. The electronic records of the identified patients were checked for the type of IBD, whether Crohn's disease (CD) or ulcerative colitis (UC), type of biological agent, route of administration (intravenous or subcutaneous), concomitant immunosuppressive therapies, atopic status. Furthermore, the type of treatment for the AIRs and the subsequent therapy undertaken for IBD were also recorded. Results 22 AIRs were recorded out of 1911 patients (1.1%). Of these, 16/550 in patients on IFX biosimilars (2.9 %), 4/590 (0.7%) in patients on ADA biosimilars, 2/318 (0.6%) in patients on VED and 0/453 (0%) in patients on UST (Table 1). The difference in the prevalence of AIR rates observed with the different biological agents was statistically significant (p&amp;lt;0.01). 7 of 16 post-IFX AIRs were moderate-severe, with two episodes of anaphylaxis occurring in patients with CD. The two patients treated with VED experienced only mild symptoms, and no anti-reactive treatment has been used; two mild and two moderate AIRs, respectively, have been reported among patients on ADA. 12 of 22 AIRs occurred during the induction period (from the first to the third administration). 7 of 22 patients had previous allergic reactions. Conclusion Our real-world data on a large population of IBD patients treated with biologic agents confirm that AIRs are rare and occur mainly in patients treated with IFX biosimilars. Most patients who experienced AIRs were atopic. Almost all patients after AIRs changed biological agents within or out of the same biological class. Further studies are necessary to confirm our results and better characterise the profile of patients at greater risk of AIRs.

Anaphylaxis in children: Effect of age and atopic status.

Anaphylaxis is a life-threatening allergic reaction with rising incidence worldwide. Young children's limited ability to express symptoms adds unique diagnostic challenges. To study on anaphylaxis in children, including triggers, symptoms, treatment, atopic status impact, and adrenaline injection time intervals. In-patient medical records of children who were diagnosed with anaphylaxis during 2014-2021 were reviewed. One hundred thirty-three anaphylaxis events were identified. Food (47%) was the most common trigger, followed by drugs (31%), blood components (17%), insects (3%), and idiopathic causes (2%). Ten cases of refractory anaphylaxis, 2 cases of biphasic reactions, and 1 case of persistent anaphylaxis were found. There were no reported fatalities. The most common presentations involved the skin (94%), followed by the respiratory (73%), gastrointestinal (47%), and cardiovascular (42%) systems. In atopic patients, wheezing was more prominent than in those without atopy (p-value = 0.017). In the non-atopic patients, there was a higher incidence of cardiovascular symptoms, particularly hypotension (p-value = 0.001), compared to individuals with atopy. Children under 5 years old with mild-moderate anaphylaxis required more time to reach the hospital (147.0 vs. 45.0 minutes, p = 0.033) and to receive adrenaline injections (35.0 vs. 9.0 minutes, p-value = 0.017) than those with severe anaphylaxis. Childhood anaphylaxis is prevalent. Children with mild-moderate anaphylaxis experienced delays in hospital visits and adrenaline administration. Education on allergies is needed to improve the identification and prompt response to anaphylactic reactions, especially in young children.

The phenotypic heterogeneity of obese and nonobese patients with severe asthma and comparison of omalizumab-mepolizumab treatment efficiency in these patients.

In obese severe asthmatics, the degree of type 2 inflammation may vary according to their atopic status and past smoking history. In this study, we aimed to analyze the clinical and physiopathological features of obese and nonobese severe asthmatics treated with omalizumab or mepolizumab treatment. In addition we aimed to compare the clinical, spirometric outcomes and total peripheral eosinophilic count (TEC) changes after treatment with these 2 biologic agents in obese and nonobese groups. In this retrospective, cross sectional study, 121 severe asthmatic treated with biologic agents (omalizumab = 88 or mepolizumab = 33) for at least 16 weeks were included. Obese (n: 44) and nonobese severe asthmatics (n: 77) were analyzed according to whether they provided a ≥ 10 pack/years (p/y) or <10 p/y smoking history and were found to be atopic. Obese and nonobese groups were compared in terms of the change in the asthma control test, asthma attacks, TEC, and forced expiratory volume in the first second (FEV1) after treatment. In patients with ≥10 p/y smoking history, nonobese group had a significantly higher TEC compared to obese group [median (min-max) 660 cells/μL (200-1500) vs 300 cells/μL (110-770); p: 0.013]. Within the nonobese group, nonatopic patients had a significantly higher TEC compared to atopic patients [median (min-max) 1200 cells/μL (100-2100) vs 310 cells/μL (0-2730); p: 0.021]. Both biologic agents had similar effects on improving asthma control test and in reducing asthma attacks; however, mepolizumab was more effective in suppressing TEC. The improvement in FEV1 in obese group following biologic 2 agents was very similar but in nonobese group, mepolizumab was found to be superior (510 mL vs. 295 mL; p: 0.034). In our real-life study, nonobese severe asthmatics with ≥10 p/y smoking history and those that were nonatopic had higher TEC. Compared to omalizumab, mepolizumab was superior at reducing TEC in all asthmatics and in improving FEV1 in nonobese group.

Expression of periostin in aeroallergen-sensitized children with adenotonsillar hypertrophy.

The association between adenotonsillar hypertrophy (ATH) and allergies remains controversial. Periostin is an important player in allergic diseases. We aimed to investigate the expression of periostin in hypertrophic tonsils and adenoids in children. We enrolled 24 children who underwent adenotonsillectomy due to sleep-disordered breathing. They were divided into atopic and control groups according to ImmunoCAP results. The presence and location of periostin in the tonsils and adenoids were determined by immunohistochemical staining. The mRNA expression and protein levels of periostin and inflammatory cytokines were measured. Immunoreactive periostin signals were observed in the subepithelial regions and germinal centers of both tonsils and adenoids. In the subepithelial regions and germinal center, periostin signals were more prominent in both tonsils and adenoids of the atopic group than in those of the control group. Significantly, the atopic group had higher periostin mRNA expression in tonsils and adenoids than the control group. The atopic group also had higher protein level of periostin in the adenoids than the control group. Atopic children had higher TGF-β1 levels in the tonsils and adenoids than those in the controls. This study showed that periostin is present in both the tonsils and adenoids, and that its levels are increased in the adenoids of atopic children. Periostin and TGF- β1 expressions in the adenoids may be associated with the atopic status in children. Further studies are required to investigate the association between ATH and periostin in a larger number of participants.

Tumor Necrosis Factor-α (-308G>A) Gene Polymorphism and Its Association with Asthma and Atopy Status.

Asthma is one of the most prevalent chronic lung diseases that afflict genetically predisposed individuals. Certain cytokine gene polymorphisms have been associated with asthma. Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine that can modulate nonspecific inflammation to influence asthma. This study aimed to define the relationship between the TNF gene polymorphism at position -308 and asthma susceptibility, as well as atopic and non-atopic asthma. Using polymerase chain reaction with sequence-specific primers, we investigated genotype frequencies and alleles of a polymorphic gene coding for TNF-α in 86 pediatric patients with asthma and 470 healthy controls of the same race. Seventy-four patients underwent a skin prick test. The homozygous AA variant (-308, rs1800629) was the most common genotype among patients, accounting for 63.3% of all cases. In contrast, homozygous GG (-308) was significantly less prevalent in the patient group compared to the control group. TNF A (-308) allele frequency was 85.5% among asthma patients and 16.6% among healthy controls. The genotype and allele frequencies of TNF (-308 A>G, rs1800629) did not differ between atopic and non-atopic asthma. In conclusion, TNF (-308) AA and AG genotypes are associated with asthma susceptibility in Iranian children, although there was no significant difference in polymorphism between atopic and non-atopic asthma and no difference in asthma severity groups.

Nasal and Serum Immunoglobulin E Levels in Symptomatic Allergic Rhinitis Patients: A Case-Control Study.

Allergic Rhinitis (AR) is an inflammatory condition of the nasal mucosa triggered by Immunoglobulin E (IgE) mediated response to exposure to allergens. The most common symptoms are nasal obstruction, sneezing, runny nose and these in addition to swollen, itchy, red and watery eyes. Recent studies have shown highly elevated immunoglobulin E levels in the airway mucosa independently of serum IgE levels and atopic status. Nasal mucosa has intrinsic capability to produce IgE in allergic rhinitis. The study was conducted to explore the levels of nasal total IgE and serum total IgE and their correlation in symptomatic AR patients. This was a case control-study and two groups participated in the study. The first group included 203 symptomatic patients who were diagnosed in the otorhinolaryngology clinic as cases of AR, known as AR group. The second group was control group and included 203 apparently healthy volunteers without any history suggestive of AR. The associated risk factors for severe allergic symptoms were assessed by logistic regression model. The mean differences between nasal total IgE and serum total IgE levels of both groups were compared by t-test. A correlation was investigated between nasal IgE and serum IgE in both the groups. The mean level of nasal total IgE and serum total IgE was found to be 103.9 and 291.4IU/ml in AR group, respectively, and 17.5 and 67.5IU/ml in the control group, respectively. Levels of nasal total IgE and serum total IgE were significantly higher in the nasal fluids and serum of symptomatic allergic rhinitis patients than in controls (p < 0.001 and < 0.001 respectively). A logistic regression model showed severity of allergic rhinitis was significantly associated with nasal total IgE levels. The correlation of nasal total IgE levels with serum total IgE levels in the control group was found to be statistically insignificant. However a statistically positive correlation was observed between nasal total IgE and serum total IgE levels in the AR group. It is possible that nasal IgE and serum IgE interact in the pathogenesis of AR and this is evident in the current study. Nasal IgE levels should be evaluated in severe symptomatic allergic rhinitis patients. The interaction between nasal IgE to serum IgE levels should be further investigated in AR patients for other possible prevalent endotypes of AR.

Exposure to farm environment and its correlations with total IgE, IL-13, and IL-33 serum levels in patients with atopy and asthma.

The aim of the study was to evaluate total immunoglobulin E (IgE), IL-13, and IL-33 serum level in people with bronchial asthma and atopy, and in healthy control group depending on their exposure to farm animals currently and in the first year of life. The study included 174 individuals living in rural areas and in a small town. Standardized questions from the International Study of Asthma and Allergy in Childhood and The European Community Respiratory Health Survey (ECRHS) questionnaires were used to define asthma. Atopic status was verified by skin prick tests. Rural exposure including contact with livestock was verified by adequate questionnaire. Total serum IgE, IL-13, and IL-33 levels were assessed by ELISA (enzyme-linked immunosorbent assay) tests. Participants with atopy and bronchial asthma were characterized by high level of immunoglobulin E. Tendency to lower serum IgE level was observed among people reporting present contact with farm animals. Also, among those having contact with livestock in their first year of life, the analogous tendency was noticed. No difference in serum IL-13 levels in participants with asthma and atopy, and controls was observed, and there was no effect of exposure on farm animals on the concentration of IL-13. The highest IL-33 level was found in the atopic group, and the lowest in the control group. Participants currently exposed to farm animals were predisposed to have lower IL-33 serum level. Exposure of farm animals currently and in first year of life may result in a lower level of total IgE. Correlation between IL-13 and IL-33 serum levels and contact with livestock was not confirmed.

The Association Between Urinary Concentrations of Organophosphate Metabolites and Asthma-Related Outcomes Among Schoolchildren From Informal Settlements.

Objectives: There is inconsistent evidence on the relationship between pesticide exposure and childhood respiratory outcomes in non-agricultural settings. This study investigated the association between organophosphate (OP) pesticide exposure and asthma-related outcomes in children residing in four informal settlements. Methods: The study was a longitudinal study of 590 schoolchildren, with a 12months follow-up period. A standardised questionnaire adopted from the International Study of Asthma and Allergies in Childhood was administered to caregivers for child's respiratory symptoms and household characteristics. Spirometry and fractional-exhaled nitric oxide, including a phadiatop test (atopy status) and urinary dialkyl phosphate (DAP) metabolites were measured at baseline and follow-up. DAP metabolites included diethylphosphate (DEP) and dimethyl phosphate (DMP) measured at baseline and follow-up and dimethylthiophosphate (DMTP) measured only at baseline. Results: The mean ages of schoolchildren were 9.9 ± 0.91years and the overal incidence proportions of new doctor diagnosed asthma was 2.2%. No consistent patterns of increased risk of asthma outcomes with increasing DAP concentrations was found in multivariate analysis. Conclusion: Future studies with longer follow-up periods and repeated OP biomonitoring are recommended.

Mast Cell Esophagitis: A Novel Entity in Patients with Unexplained Esophageal Symptoms.

It is not known whether esophageal mast cells may be a cause of unexplained esophageal symptoms. We aimed to determine the prevalence of esophageal mastocytosis in patients without other underlying causes of symptoms and assess the relationship between symptoms and mast cells. In this retrospective study, we identified adults with esophageal symptoms, a normal endoscopy, normal esophageal biopsies, and no definitive diagnosis during clinical evaluation. We quantified mast cell density (mast cells/mm2) in archived esophageal biopsies using tryptase immunohistochemistry, and compared mast cell levels by clinical features and physiologic testing. In the 87 patients identified (mean age 37, 72% female, 63% white, 92% non-Hispanic), common symptoms were dysphagia (76%), heartburn (71%), and chest pain (25%). Overall, the mean esophageal epithelial mast cell count was 83.0 ± 51.8 mast cells/mm2; 60% of patients had ≥ 60 mast/mm2, and 17% had ≥ 120 masts/mm2. There were no differences in mast cell counts by type of esophageal testing. Mast cell levels did not differ significantly by type of symptoms, atopic status, medications, smoking status, or alcohol use. There were also no major differences in clinical characteristics by mast cell quartiles or thresholds. In conclusion, esophageal mast cell infiltration was common in patients with symptoms unexplained by prior testing, and levels were higher than previously published values for patients with no underlying esophageal condition. Mast cell esophagitis could be a novel cause of unexplained esophageal symptoms in a subset of patients, though it reamins to be determined if such patients benefit from mast cell-targeted treatment.