Chronic Atopic Disease Research Articles

Insights from Overviewing Selective International Guidelines for Pediatric Asthma.

Asthma is a chronic atopic and inflammatory bronchial disease characterized by recurring symptoms and, episodic reversible bronchial obstruction and easily triggered bronchospasms. Asthma often begins in childhood. International guidelines are widely accepted and implemented; however, there are similarities and differences in the management approaches. There is no national guideline in many cities in Asia. This review aims to provide a practical perspective on current recommendations in the management of childhood asthma, specifically in the following aspects: diagnosis, classification of severity, treatment options, and asthma control, and to provide physicians with up-to-date information for the management of asthma. We used the PubMed function of Clinical Queries and searched keywords of "Asthma", "Pediatric," AND "Guidelines" as the search engine. "Clinical Prediction Guides", "Etiology", "Diagnosis", "Therapy," "Prognosis," and "Narrow" scope were used as filters. The search was conducted in November 2022. The information retrieved from this search was used in compiling the present article. Diagnosis is clinically based on symptom pattern, response to therapy with bronchodilators and inhaled corticosteroids, and spirometric pulmonary function testing (PFT). Asthma is classified in accordance with symptom frequency, peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), atopic versus nonatopic etiology, where atopy means a predisposition toward a type 1 hypersensitivity reaction. Asthma is also classified as intermittent or persistent (mild to severe). Unfortunately, there is no disease cure for asthma. However, symptoms can be prevented by trigger avoidance and suppressed with inhaled corticosteroids. Antileukotriene agents or long-acting beta-agonists (LABA) may be used together with inhaled corticosteroids if symptoms of asthma are not controlled. Rapidly worsening symptoms are usually treated with an inhaled short-acting beta-2 agonist (SABA, e.g., salbutamol) and oral corticosteroids. Intravenous corticosteroids and hospitalization are required in severe cases of asthma attacks. Some guidelines also provide recommendations on the use of biologics and immunotherapy. Asthma is diagnosed clinically, with supporting laboratory testing. Treatment is based on severity classification, from intermittent to persistent. Inhaled bronchodilator and steroid anti-inflammatory form the main stay of management.

Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.

Gastrointestinal involvement of primary skin diseases

Less is known about gastrointestinal (GI) involvement of primary skin diseases due to the difference in embryology, histology, microbiology and physiology between integument and alimentary tract. Oesophagus, following the oropharyngeal mucosa, is the most common GI segment affected by primary skin diseases, especially by eosinophilic oesophagitis, lichen planus and autoimmune bullous dermatoses like pemphigus vulgaris, mucosal membrane pemphigoid and epidermolysis bullosa acquisita. Eosinophilic oesophagitis is an emerging chronic atopic disease with oesophageal dysfunction as the typical presentation, and oesophageal narrowing, rings and stricture as late complications. Oesophageal lichen planus mainly involves the proximal to mid-oesophagus in elderly aged women with long-term oral mucosal lesions. In acute attack of pemphigus vulgaris, oesophageal involvement is not uncommon but often neglected and may cause sloughing oesophagitis (oesophagitis dissecans superficialis) with acute GI bleeding in rare cases. GI manifestation of hereditary bradykininergic angio-oedema with colicky acute abdomen mostly affects small intestine, usually in the absence of pruritus or urticaria, and is more severe and long-lasting than the acquired histaminergic form. Strong evidence supports association between inflammatory bowel disease, especially Crohn disease, and hidradenitis suppurativa/acne inversa. Patients with vitiligo need surveillance of autoimmune liver disease, autoimmune atrophic gastritis or coeliac disease when corresponding symptoms become suspect. Melanoma is the most common primary tumour metastatic to the GI tract, with small intestine predominantly targeted. Gastrointestinal involvement is not uncommon in disseminated mycosis fungoides. Extramammary Paget's disease is an intraepidermal adenocarcinoma of controversial origin, and a high association between the anogenital occurrence and colorectal adenocarcinoma has been reported. As GI tract is the largest organ system with multidimensional functions, dermatologists in daily practice should be aware of the gastrointestinal morbidities related to primary skin diseases for an early diagnosis and treatment.

Family functioning according to clusters of family management styles in Korean families of children with chronic atopic disease: A cross-sectional study

BackgroundChronic allergic diseases in children are often linked with behavioral problems, poor daily living, negative perceptions of health, and low life satisfaction. ObjectivesThis study aimed to propose clusters of family management styles in the Korean families of children with chronic atopic disease, including allergic asthma, atopic dermatitis, and/or allergic rhinitis and examine the level of family functioning according to these clusters. DesignCross-sectional study. SettingsA university-level hospital in metropolitan Seoul, South Korea. ParticipantsParents of children with chronic atopic disease. MethodsThis study included 146 participants. The Korean version of the Family Management Measure and the Korean Family Functioning Scale were used to assess family management styles and family functioning, respectively. Data were analyzed using SPSS 24.0 using descriptive statistics, agglomerative hierarchical clustering with Ward's method prior to k-means clustering, k-means clustering analysis, analysis of variance, and chi-squared test. ResultsFour clusters of family management styles were identified as follows: stable-resilient, less committed, parents’ mission, and challenging. Among all participants, 19.9%, 30%, 20.6%, and 29.5% belonged to each of these clusters, respectively. The level of family functioning significantly differed between the four clusters, with the stable-resilient cluster having the highest mean level and the challenging cluster having the lowest mean level. Parents’ perceived the complexity of self-managing their child's condition as one of the factors differentiating the level of family functioning of each cluster. ConclusionsThis study identified four clusters of family management styles and showed that each cluster was associated with a different level of family functioning. The unique characteristics of the four clusters may be helpful in providing individualized care and promoting positive family functioning in families with children having chronic atopic disease.

Updates to the Current Understanding of the Relationship Between Allergy and Chronic Sinusitis

To examine the relationship of chronic rhinosinusitis (CRS) and atopic disease. CRS with nasal polyps (CRSwNP) has been shown to be associated with high aeroallergen sensitivity and local allergic response, but with no difference in imaging, symptomatic severity, or disease recurrence rates in atopic vs. non-atopic individuals. There is conflicting evidence for CRS without nasal polyps (CRSsNP) with regard to the relationship with atopic disease. There may, however, be differential molecular profiles between atopic and non-atopic patients with CRSsNP. There is no consensus as to whether atopic disease is related to CRS. Recent studies have shown that atopic disease may be implicated in pathogenesis, but may not contribute to clinical severity. It should, however, be noted CRS likely has multifactorial etiologies. Finally, specific subtypes of CRS, such as central compartment atopic disease (CCAD), are likely atopy driven and allergic management should play a key role in treatment of these patients.

The Association between Maternal Stress and Childhood Eczema: A Systematic Review.

Eczema is a chronic atopic disease that is highly prevalent among children worldwide. Identification of factors that may contribute to childhood eczema is needed in order to develop strategies in its prevention. Over the past decade, accumulating evidence has suggested a potential correlation between the experience of stress by mothers and the risk of eczema development in their child. The present review attempts to provide an overview of the studies that contribute data on this correlation. The literature search was conducted using five databases, resulting in the inclusion of eleven studies in the review. The findings of these studies were summarized narratively. Further, an appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Overall, the included studies showed that a positive correlation exists between the experience of stress among mothers and eczema risk of their child. The findings highlight the importance of the implementation of stress reduction programs for pregnant women and those in their postpartum period within communities in order to enable these individuals to relieve stress effectively.

From genetics to treatment of eosinophilic esophagitis.

Eosinophilic Esophagitis (EoE) is an emerging chronic atopic disease. Recent advances in understanding its genetic and molecular biology pathogenesis may lead to a better management of the disease EoE is an atopic disease. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and n-IgE-mediated reaction to food and/or environmental allergens. Epidemiological studies show that EoE is an atopic disease with a strong genetic component. Genetic studies have shown that EoE is associated with single nucleotide polymorphism on genes, which are released by the epithelium and important in atopic inflammation such as thymic stromal lymphopoietin located (TSLP) close to the Th2 cytokine cluster [interleukin (IL)-4, IL-5, IL-13] on chromosome 5q22, Calpain 14, EMSY, and Eotaxin3. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient, but also to prevent complications such as esophageal stricture and food impaction. EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance. The new understanding of EoE may lead to more specific and definitive treatments of EoE.

Eosinophilic Esophagitis and Gastroenteritis.

Eosinophilic gastrointestinal disease (EGID) can be classified as eosinophilic esophagitis (EoE) when the eosinophilia is limited to the esophagus or as eosinophilic gastritis (EG) if it is limited to the gastric tract, eosinophilic colitis (EC) if it is limited to the colon, and eosinophilic gastroenteritis (EGE) if the eosinophilia involves one or more parts of the gastrointestinal tract. EoE is by far the most common EGID. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammation triggered often by food allergens. EoE diagnosis is done if an esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf). Globally accepted long-term therapies for EoE are the use of swallowed inhaled steroids or food antigen avoidance. The treatment of EoE is done not only to control symptoms but also to prevent complications such as esophageal stricture and food impaction. EGE cause non-specific gastrointestinal (GI) symptoms and are diagnosed if esophagogastroduodenoscopy (EGD)/colonoscopy show eosinophilia in one or more parts of the GI tract. They are rare diseases with an unclear pathogenesis, and they are poorly defined in terms of diagnostic criteria and treatment. Before initiating treatment of any EGE, it is imperative to conduct a differential diagnosis to exclude other causes of hypereosinophilia with GI localization. EGE are often poorly responsive to therapy and there is no commonly accepted long-term treatment. EG has many characteristics similar to EoE, including the fact that it is often due to a food allergen-driven Th2 inflammation; transcriptome analysis however shows that it is more a systemic disease and has a different gene signature than EoE. EC is a benign form of delayed food allergy in infant and is instead a difficult-to-treat severe inflammatory condition in older children and adults. EC in the latter groups can be a manifestation of drug allergy or autoimmune disease. Overall EGE, EC, and EG are rare and are a diagnosis of exclusion until more common causes of eosinophilia have been excluded.

Eosinophilic Esophagitis: A Comprehensive Review.

Eosinophilic esophagitis (EoE) is an emerging chronic atopic clinical-pathologic disease with an estimated prevalence of 1/1000 similar to the one of Crohn's diseases. Usually, EoE is firstly suspected due to symptoms that are caused by esophageal dysfunction and/or fibrosis. EoE diagnosis is confirmed if the esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf) as a peak value in one or more of at least four specimens obtained randomly from the esophagus. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies, and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and non-IgE-mediated reaction to food and/or environmental allergens. Recently published genetic studies showed also that EoE is associated with single nucleotide polymorphism (SNP) on genes which are important in atopic inflammation such as thymic stromal lymphopoietin (TSLP) located close to the Th2 cytokine cluster (IL-4, IL-5, IL-13) on chromosome 5q22. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient but also to prevent complications such as esophageal stricture and food impaction. EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance.

Immunological Efficiency of MNRI Program at Treatment of Respiratory Diseases

Immunological Efficiency of MNRI Program at Treatment of Respiratory Diseases

Type I Interferon Regulates Acute IL-5 and IL-13 Expression in Human Memory CD4+ T Cells

Type I Interferon (IFN-α/β) is an innate cytokine important for fighting infections and is used to treat a variety of diseases. Here, we show that IFN-α/β plays a role in shaping the Th2 response in humans. We propose that activation of this Th2 regulatory pathway with IFN-α/β, or other antagonist with fewer side effects, will be helpful in the treatment of severe asthma and other chronic atopic diseases.

IgE sensitization to the nonspecific lipid-transfer protein Ara h 9 and peanut-associated bronchospasm.

Allergen component analysis is now available in many laboratories. The aim of this study was to examine the possible association between peanut allergen IgE components and severity of clinical reactions in patients with a history of peanut allergy. Data and sera collected from 192 patients within the Manchester Allergy Research Database and Serum Bank were used in this retrospective study. Sensitization to peanut specific IgE and Ara h 1, 2, 3, and 8 peanut IgE components, as measured by fluoroenzyme immunoassay, was not associated with anaphylaxis. In contrast, sensitization to the lipid-transfer protein Ara h 9 was significantly more prevalent in patients with peanut-associated bronchospasm (26% versus 9% of patients), even after adjusting for potential confounding effects of age, gender, and severity of concomitant chronic atopic diseases. Patients who were sensitized to Ara h 9 were more likely to have ingested rather than just have had skin contact with peanut and have a more rapid onset of symptoms. These results are consistent with observations that sensitization to heat and protease resistant lipid-transfer protein components of hazelnut, grains, and fruit is predictive of anaphylaxis.

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women's infertility.

Btk-dependent Rac activation and actin rearrangement following FcεRI aggregation promotes enhanced chemotactic responses of mast cells

Mast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E(2), is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (FcεRI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)Cγ-mediated Ca(2+) mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF, adenosine and PGE(2) were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk(-/-) mice. There were corresponding decreases in the PLCγ-mediated Ca(2+) signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses.

Patients' report on how endometriosis affects health, work, and daily life

The objective of this study was to assess the burden of endometriosis by obtaining patient-reported outcome data describing the experience of living with this disease. Survey data from 107 women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work, and daily life.

Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions

To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis, are associated with endometriosis lesions. Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction-based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. University hospital. Seventy individual patients with and without endometriosis. Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.

Personality characteristics in chronic and non-chronic allergic conditions

In psycho-allergological research, the potential relevance of personality factors in the maintenance and exacerbation of atopic symptoms is still a matter of debate. The present study aimed to assess personality dimensions in chronic atopic disease, i.e. atopic dermatitis (AD) and in acute manifestation of atopy (seasonal allergic rhinitis, SAR). Further, the association of a potentially atopy-specific personality profile with atopy-relevant biological stress responses should be evaluated. Subjects suffering from AD ( n = 36), or SAR ( n = 20) and non-atopic controls ( n = 37) were investigated. To determine different personality domains, Spielberger’s State-Trait Anxiety Inventory (STAI), the Questionnaire for Competence and Control (FKK) and the Questionnaire for Stress Vulnerability (MESA) were administered. To assess the relation between these personality dimensions and biological stress responses, atopics and non-atopic controls were exposed to a standardized laboratory stressor (Trier Social Stress Test, TSST). Endocrine (cortisol, ACTH), immune (total IgE, leukocyte subsets) and physiological (heart rates) measures were recorded before and after the stress test. When compared to healthy controls, AD and SAR patients showed significantly higher trait anxiety (STAI) and stress vulnerability in situations characterized by failure, job overload and social conflicts (MESA). Moreover, AD subjects scored significantly lower in self-competence and self-efficacy (FKK) as well as in recreation ability (MESA). No difference trait anxiety and stress vulnerability could be detected between AD and SAR subjects. Pearson correlational analyses yielded no significant correlation between the different personality domains and the endocrine, physiological and immunological stress responses. However, stress-induced increase in eosinophil number was significantly correlated with the perceived self-competence/self-efficacy in SAR patients.

Autosensitization as a Pathomechanism in Asthma

Recent observations indicate that autoimmune disorders and allergies are more closely connected to each other than traditionally considered. Both diseases are characterized by a break of immunological tolerance and in both Th1- and Th2-driven mechanisms may be involved. Moreover, patients suffering from severe chronic atopic diseases have been shown to develop autoreactive antibodies and vice versa autoreactive IgE antibodies may contribute to the perpetuation of allergic immune responses. However, animal models for the investigation of the underlying mechanisms have not been available so far. Here we demonstrate that allergic sensitization and subsequent airway aerosol challenge of mice to a potential autoantigen leads to an allergic airway inflammation and chronic exposure of sensitized mice to a foreign allergen induces autoreactive antibodies. Thus, autoreactive immune mechanisms may be induced either by molecular mimicry or as a consequence of chronic allergic inflammatory processes and these reactivities may then possibly contribute to the perpetuation of allergic immune responses even in the absence of exogenous allergens and to the development of autoimmune diseases.

Immunopathology of atopic dermatitis

Immunopathology of atopic dermatitis

The influence of childhood infections and vaccination on the development of atopy: A systematic review of the direct epidemiological evidence

Background The ‘hygiene hypothesis’ has been used to justify a belief common among homeopaths, that the suppression of childhood infections and immunisation may lead to the development of chronic atopic diseases. Objectives To analyse the influence of childhood infections and immunisation on the development of atopy. Methods Qualitative systematic review of direct epidemiological evidence (Medline 1993–2004) concerning the influence of childhood infections and immunisation on the development of atopy and discussion based on homeopathy. Conclusions (1) Childhood infections do not protect against atopy; on the contrary, they increase the risk of allergic diseases, in agreement to Hahnemann's observations, which included epidemic diseases among the factors capable of stimulating the development of chronic diseases. (2) Vaccination is not a risk factor for atopy, notwithstanding the allergenic effect of some vaccines.