scholarly journals Precision Medicine in House Dust Mite-Driven Allergic Asthma

2020 ◽  
Vol 9 (12) ◽  
pp. 3827
Author(s):  
Ibon Eguiluz-Gracia ◽  
Francisca Palomares ◽  
Maria Salas ◽  
Almudena Testera-Montes ◽  
Adriana Ariza ◽  
...  

House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA.

2017 ◽  
Vol 41 (1) ◽  
pp. 34-41 ◽  
Author(s):  
Erhan Zeytun ◽  
Salih Dogan ◽  
Fatih Ozcicek ◽  
Edhem Unver

2021 ◽  
Author(s):  
Weifeng Tang ◽  
Ming Dong ◽  
Fangzhou Teng ◽  
Jie Cui ◽  
Xueyi Zhu ◽  
...  

Abstract Background: Studies have indicated that allergens such as house dust mites (HDM) in the environment could induce allergic asthma. Ferroptosis is a newly discovered regulatory cell death characterized by aberrant lipid peroxidation and accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological progress of asthma remains to be elucidated. In this study, we used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and the underlying mechanisms. Methods: Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation and mucus secretion, IgE and cytokine levels as well as inflammatory cell counts in bronchalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS, glutathione (GSH) levels and changes in ferroptosis pathway proteins in the lung were also determined. Results: HDM exposure increased AHR significantly, and enhanced inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE level in BALF, lung eosinophilia, and a concomitant increase in IL-13 and IL-5 in BALF were observed. HDM inhalation increased ROS and decreased GSH level in the lung. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blot analysis demonstrated that activity of glutathione peroxidase 4 (GPX4) and catalytic subunit solute carrier family 7 member 11 (SLC7A11) decreased significantly, and protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and 15 Lipoxygenase 1 (15-LO1) upregulated prominently compared with mice in normal control group. Conclusions: These in all indicated that the AHR, airway inflammation, lipid peroxidation and ROS level increased in HDM-induced asthma, and HDM inhalation caused ferroptosis in the lungs, which helped to form a better understanding of the pathogenesis of allergic asthma and targeted treatment strategies.


Author(s):  
Catalina Gómez ◽  
Judit Barrena ◽  
Vanesa García-Paz ◽  
Ana M. Plaza ◽  
Paula Crespo ◽  
...  

AbstractEvidence regarding asthma’s impact on children’s daily lives is limited. This prospective and cross-sectional, observational, multicenter study assessed school/work and activity impairment in children and adolescents with allergic asthma and their caregivers and allergen immunotherapy (AIT) effects. Included patients were schooled children and adolescents (5 to 17 years) with allergic asthma due to house dust mites (HDM). Impairment of school/work (i.e., absenteeism and presenteeism) and activity was measured in patients and their caregivers using the Work Productivity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI + CIQ:AS). HDM allergic patients with school impairment received subcutaneous AIT with a MicroCrystalline Tyrosine-associated allergoid. WPAI + CIQ:AS and effectiveness variables were compared between baseline and 1-year post-AIT. Of the 113 patients included, 59 (52.2%) and 51 (45.1%) showed school and activity impairment, respectively, missing a mean (SD) of 37.6 (24.4) % and 42.6 (25.6) % of school and activity time, respectively. Twenty-six (23%) caregivers reported activity impairment and, of the 79 (69.9%) employed, 30 (38%) reported work impairment. Of the 65 patients with school/activities impairment, 41 (63.1%) received AIT, of which 21 (51.2%) completed 1 year of treatment. Effectiveness variables and WPAI + CIQ:AS significantly improved: Mean (SD) school impairment decreased from 39.7 (26.7) to 2.1 (7.1) % (p < 0.001) and activity impairment from 46.2 (34.6) to 1.4 (3.6) % (p < 0.001).Conclusion: Allergic asthma due to HDMs results in school/work and activity impairment in children and adolescents and their caregivers. One year of AIT provided clinical benefits and reduced school and activity impairment. What is Known:• Allergic asthma impairs children’s school performance and daily activities.• Allergen immunotherapy modifies allergic disease course and ameliorates its symptoms. What is New:• Asthma symptoms due to allergy to house dust mites impair children’s school attendance and productivity and daily activity and their caregivers’ work performance and daily lives.• Allergen immunotherapy with a house dust mite MicroCrystalline Tyrosine (MCT)-associated allergoid seems to provide clinical benefits, associated with decreased school and activity impairment, supporting it as an effective treatment option.


2021 ◽  
Vol 26 (1) ◽  
pp. 75-84
Author(s):  
Amandeep Kaur Dhaliwal ◽  
Devinder Singh ◽  
Ramanpreet Kaur Randhawa ◽  
Atinderpal Singh

Asthma is a common problem that affects about 20 million peoples in India and can be often under-diagnosed or misdiagnosed. It can be allergic or non-allergic though the former type is more common and prevalent. Allergic asthma can be triggered by many allergens and house dust mites (HDM) are one of the common indoor allergens. The present study emphasizes the significance of house dust mites in allergic asthmatic subjects which is based on 115 asthmatic subjects in Punjab, India. For the quantification and the estimation of total serum Immunoglobulin E and HDM specific IgE, a mixture of 14 allergens and a mixture of two mite allergens viz. Dermatophagoides pteronyssinus and D. farinae were used respectively. Total and specific IgE levels were detected on ImmunoCAP Phadia 100. A statistically significant correlation between total and HDM specific IgE levels of 115 asthmatic subjects was found as compared to control group of 30 non-allergic individuals. The specific IgE levels of 54.78% subjects against the allergen of two mite species were found to be positive. Dust samples were taken from various localities of the houses to identify the diversity of house dust mites which were responsible for allergic asthma. Five common house dust mite species viz. D. pteronyssinus Trouessart, D. farinae Hughes, D. microceras Griffiths and Cunnington, D. aureliani Fain and Euroglyphus maynei Cooreman were identified from the dust. The present study observed that total IgE levels were higher with higher specific IgE levels against the mixture of two mite allergens viz. D. pteronyssinus and D. farinae in the blood serum.  D. pteronyssinus was the most abundant and prevalent mite species followed by D. farinae. Therefore, present study concluded that HDM specific IgE levels against the mite allergen of D. pteronyssinus and D. farinae in the serum of allergic asthmatic subjects were found to be higher because of the higher prevalence of these two mites (D. pteronyssinus i.e. 69.80% and D. farinae i.e. 20.72%) in the house of allergic asthmatic subjects as compared to other identified mites.


1995 ◽  
Vol 182 (5) ◽  
pp. 1537-1544 ◽  
Author(s):  
C R Hewitt ◽  
A P Brown ◽  
B J Hart ◽  
D I Pritchard

Asthma is a chronic life-threatening disease of worldwide importance. Although allergic asthma and related atopic conditions correlate strongly with immune sensitization to house dust mites, it is unclear why antigens from mites provoke such powerful allergic immune responses. We have characterized the protease activity of Der p I, the group I protease allergen of the house dust mite Dermatophagoides pteronyssinus, and here report that it cleaves the low-affinity immunoglobulin (Ig) E Fc receptor (CD23) from the surface of human B lymphocytes. Der p I selectively cleaves CD23 and has no effect on the expression of any other B cell surface molecules tested. We speculate that this loss of cell surface CD23 from IgE-secreting B cells may promote and enhance IgE immune responses by ablating an important feedback inhibitory mechanism that normally limits IgE synthesis. Furthermore, since soluble CD23 is reported to promote IgE production, fragments of CD23 released by Der p I may directly enhance the synthesis of IgE. alpha 1-Antiprotease, a pulmonary antiprotease, is also shown to inhibit the cleavage of CD23 by Der p I. This may be significant in the etiopathogenesis of asthma, because other indoor pollutants associated with asthma are known to potently inhibit this antiprotease. These data suggest that the proteolytic activity of Der p I, the group I allergen of the house dust mite D. pteronyssinus, is mechanistically linked to the potent allergenicity of house dust mites. Furthermore, inhibition of Der p I by alpha 1-antiprotease suggests a mechanism by which confounding factors, such as tobacco smoke, may act as a risk factor for allergic asthma.


2017 ◽  
Vol 4 (2) ◽  
pp. 72-78
Author(s):  
Olena Sharikadze

Sharikadze O.V.Background. This study determined the efficacy of sublingual allergen–specific immunotherapy (SLIT) in Ukrainian children younger than 5 years of age with allergic rhinitis and bronchial asthma sensitized to house dust mite allergens. Methods. A cohort prospective study was conducted over a two years period with assessment of the sensitization towards inhalant allergens, measured in-vivo by wheal size and number of positive reactions on the standard skin prick test (SPT). SPSS was used to analyse any statistical correlation. Results. A total of 125 atopic asthma or/and allergic rhinitis with the mean age of 4.11 ±0.83 who were sensitized to house dust mites Dermatophagoides pteronyssinus and/or Dermatophagoides farina were included. 47 children received two-years SLIT to treat house dust mite allergies using standardized extract of sublingual allergens containing a mixture of house dust mites (Der.  pteronyssinus and Der. farinae) in the correlation of 1(0,175 НЕР):1(0,175 НЕР) (Diater, Spain). These patients were mono-sensitized with Der. pteronyssinus and Der. farinae or were SPT poly-sensitized, but these patients only had house dust mite allergy symptoms. In this group the assessment of clinical efficacy of SLIT showed the significant differences in VAS before treatment and 6 months after its receiving. The symptom “nasal obstruction” was assessed as 2.3±-1.6 points  at the beginning of the therapy, and the data reduced almost twice (1.3±-1.1); Р <0,05 after 6  months of SLIT;  then (12 and 24 months) it decreased to 0.91±0.9 and 0.34±0.5; Р <0,01, correspondingly. Conclusion. This study has shown that using of SLIT in atopic asthma or/and allergic rhinitis children under 5 year sensitized to house dust mites is an effective and safe treatment method and allows to quickly (over the first 6 months of SLIT) control the symptoms. The data of comparative analysis in the group of patients who didn’t receive SLIT has pointed to high frequency of disease symptom occurrence after the end of baseline therapy.KeyWords: sublingual allergen-specific immunotherapy, children, bronchial asthma, allergic rhinitis, sensitization, allergens, Diater  ОСОБЛИВОСТІ ЛІКУВАННЯ ДІТЕЙ ДОШКІЛЬНОГО ВІКУ, СЕНСІБІЛІЗОВАНИХ ДО АЛЕРГЕНІВ ДОМАШНЬОГО ПИЛУШарикадзе О.В.Це дослідження визначило ефективність сублингвально алерген-специфічної імунотерапії (SLIT) українських дітей молодше 5 років з алергічним ринітом та бронхіальною астмою, сенсибілізованих до алергенів пилових кліщів. Методи. Проспективне дослідження когорти проводилося протягом двох років з оцінкою сенсибілізації до інгаляційних алергенів, виміряної in-vivo за розміром пухирів і кількості позитивних реакцій на стандартному тесті на шкірі (SPT). Для аналізу статистики використовувався пакет SPSS. Результати. Обстежено 125 дітей (середній вік 4,11 ± 0,83 років) з атопічною астмою та/або алергічним ринітом, які були сенсибілізовані до домашніх пилових кліщів Dermatophagoides pteronyssinus та/або Dermatophagoides farina. 47 дітей отримали дворічний курс SLIT з використанням стандартизованого екстракту сублінгвальних алергенів, що містять суміш кліщів домашнього пилу (Der. Pteronyssinus і Der. Farinae) в співвідношенні 1 (0,175 НЕР): 1 (0,175 НЕР) (Діатер, Іспанія). Пацієнти були моносенсібіровани Dermatophagoides pteronyssinus і / або Dermatophagoides farina або були полісенсібілізовані (за SPT), однак симптоми розвивалися тільки на домашній пил. У цій групі оцінка клінічної ефективності SLIT показала значні відмінності до лікування і через 6 місяців після його отримання. Симптом «носової обструкції» оцінювався як 2,3 ± 1,6 бала на початку терапії і зменшувалися майже в два рази (1,3 ± 1,1); Р <0,05 після 6 місяців SLIT. Потім (12 і 24 місяці) він знизився до 0,91 ± 0,9 і 0,34 ± 0,5; Р <0,01, відповідно. Висновок. Дослідження показало, що використання SLIT при атопічній астмі та/або алергічному риніті у дітей до 5 років, сенсибілізованих до домашніх пилових кліщів, є ефективним і безпечним методом лікування і дозволяє швидко (протягом перших 6 місяців SLIT) контролювати симптоми. Дані порівняльного аналізу в групі пацієнтів, які не отримували SLIT, вказують на високу частоту виникнення симптомів хвороби після закінчення базової терапії.Ключові слова: сублінгвальна алерген-специфічна імунотерапія, діти, бронхіальна астма, алергічний риніт, сенсибілізація, алергени, Діатер. ОСОБЕННОСТИ ЛЕЧЕНИЯ ДЕТЕЙ ДОШКОЛЬНОГО ВОЗРАСТА, СЕНСИБИЛИЗИРОВАННЫХ АЛЛЕРГЕНАМИ ДОМАШНЕЙ ПЫЛИШарикадзе Е.В.Это исследование определило эффективность сублингвальной аллерген-специфической иммунотерапии (SLIT) украинских детей моложе 5 лет с аллергическим ринитом и бронхиальной астмой, сенсибилизированных к аллергенам пылевых клещей. Методы. Проспективное исследование когорты проводилось в течение двух лет с оценкой сенсибилизации к ингаляционным аллергенам, измеренной in-vivo по размеру волдырей и количеству положительных реакций на стандартном тесте на коже (SPT). Для анализа статистики использовался пакет SPSS. Результаты. Обследованы 125 детей (средний возраст 4,11 ± 0,83 лет) с атопической астмой и/или аллергическим ринитом, которые были сенсибилизированы к домашним пылевым клещам Dermatophagoides pteronyssinus и/или Dermatophagoides farina. 47 детей получили двухлетний курс SLIT с использованием стандартизованного экстракта сублингвальных аллергенов, содержащих смесь клещей домашней пыли (Der. Pteronyssinus и Der. Farinae) в соотношении 1 (0,175 НЕР): 1 (0,175 НЕР) (Диатер, Испания). Пациенты были моносенсибированы Dermatophagoides pteronyssinus и/или Dermatophagoides farina или были полисенсибилизированы (по SPT), однако симптомы развивались только на домашнюю пыль. В этой группе оценка клинической эффективности SLIT показала значительные различия до лечения и через 6 месяцев после его получения. Симптом «носовой обструкции» оценивался как 2,3 ± -1,6 балла в начале терапии и уменьшались почти в два раза (1,3 ± -1,1); Р <0,05 после 6 месяцев SLIT. Затем (12 и 24 месяца) он снизился до 0,91 ± 0,9 и 0,34 ± 0,5; Р <0,01, соответственно. Вывод. Исследование показало, что использование SLIT при атопической астме или/или аллергическом рините детей до 5 лет, сенсибилизированных к домашним пылевым клещам, является эффективным и безопасным методом лечения и позволяет быстро (в течение первых 6 месяцев SLIT) контролировать симптомы. Данные сравнительного анализа в группе пациентов, которые не получали SLIT, указывают на высокую частоту появления симптомов болезни после окончания базовой терапии.Ключевые слова: сублингвальная аллерген-специфическая иммунотерапия, дети, бронхиальная астма, аллергический ринит, сенсибилизация, аллергены, Диатер.


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