Allergy, Asthma & Immunology Research最新文献

Purpose: Asthma is a common chronic inflammatory respiratory tract disease with high morbidity and mortality. The global trends in asthma burden remain poorly understood, and asthma incidence has increased during the worldwide coronavirus disease 2019 (COVID-19) pandemic. This study aimed to provide a comprehensive view of the global distribution of asthma burden and its attributable risk factors from 1990 to 2019.

Methods: Based on the Global Burden of Disease Study 2019 Database, asthma incidence, deaths, disability-adjusted life years (DALYs), the corresponding age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), age-standardized DALY rate, and estimated annual percentage change were analyzed according to age, sex, sociodemographic index (SDI) quintiles, and locations. Risk factors contributing to asthma deaths and DALYs were also investigated.

Results: Globally, the asthma incidence increased by 15%, but deaths and DALYs decreased. The corresponding ASIR, ASDR, and age-standardized DALY rate also decreased. The high SDI region had the highest ASIR, and the low SDI region had the highest ASDR. The ASDR and age-standardized DALY rate were negatively correlated with the SDI. The low-middle SDI region, particularly South Asia, showed the highest asthma-related deaths and DALYs. The incidence peak was under 9 years old, and more than 70% of all deaths occurred in the population over 60 years old. Smoking, occupational asthmagens, and a high body mass index were the main risk factors for asthma-related mortality and DALYs, and their distributions varied between sexes.

Conclusions: Globally, the asthma incidence has increased since 1990. The greatest asthma burden is borne by the low-middle SDI region. The 2 groups that need special attention are those under 9 years old and those over 60 years old. Targeted strategies are needed to reduce the asthma burden based on geographic and sex-age characteristics. Our findings also provide a platform for further investigation into the asthma burden in the era of COVID-19.

The allergy epidemic has been attributed to environmental influences related to urbanization and the modern lifestyle. In this regard, various theories exploring the role of microbes (hygiene, old friends, microbiota, and biodiversity hypotheses), and the epithelial barrier (epithelial, dual allergen exposure and vitamin D hypotheses) have been proposed. These hypotheses have guided clinical studies that led to the formulation of intervention strategies during the proposed window of opportunity dubbed as the "first thousand days." The most significant intervention is a paradigm shift from allergen avoidance to early introduction of allergenic foods, particularly egg and peanut, around 6 months of age for the prevention of food allergy. This recommendation has been adopted globally and included in allergy prevention guidelines. Other strategies with less robust clinical evidence include: encouraging a healthy balanced diet, rich in fish, during pregnancy; continuing allergenic food intake during pregnancy and lactation; vitamin D supplementation in pregnant women with asthma; discouraging social indications for caesarean section delivery; judicious use of antibiotics in early childhood; daily emollient use from birth in high risk babies; and avoiding cow's milk formula use in the first week of life. However, if early supplementation with cow's milk formula is required, continuing at least 10 mL of formula daily until age 2 months may be considered. Translating these strategies to public health and clinical practice is still a work in progress. Long-term population studies are crucial to assess the feasibility of these measures on allergy prevention.

Purpose: Chronic cough (CC) is associated with health-related quality of life (HRQoL) impairment. However, the determinants of HRQoL are under-investigated.

Methods: Patients aged 19-80 years with CC were prospectively recruited from 10 referral clinics. Comparisons were made with age- and sex-matched controls (1:4 ratio) selected from a Korean general population survey database; 1) a group without current cough (non-cough controls) and 2) another group without major chronic illnesses (healthy controls). HRQoL was assessed using the EuroQoL 5-dimension (EQ-5D) index. In CC patients, cough-specific patient-reported outcomes (PROs) were additionally measured. Cross-sectional analyses were performed to evaluate demographic and clinical parameters associated with the EQ-5D index of CC patients.

Results: A total of 200 CC patients (137 newly referred with CC and 63 refractory or unexplained CC [RUCC] patients), 800 non-cough controls, and 799 healthy controls were analyzed. The EQ-5D index of CC patients was significantly lower than that of non-cough controls or healthy controls (0.82 ± 0.14 vs 0.92 ± 0.14/0.96 ± 0.08; P < 0.001, respectively). The index was also associated with older age (≥ 60 years), female sex, and comorbidities such as asthma or depression. Among the patients with CC, the index was significantly lower in patients with RUCC than in those with newly referred CC, being treated with codeine or cough neuromodulators, or with cough-related fatigue. In Spearman analyses, the EQ-5D index correlated with cough-specific quality of life and cough severity scores, not with throat sensation or cough trigger scores.

Conclusions: The HRQoL impairment of CC patients was associated with older age, female sex, and comorbidities but it was also affected by cough severity, complications, treatments, and treatment responses. Longitudinal studies are warranted to further understand and improve the HRQoL of CC patients.

Purpose: Increased evidence has shown that aerobic exercise reduces airway hyperresponsiveness in asthmatic individuals. However, the underlying mechanisms of action remain elusive. This study aimed to investigate the effect of exercise on airway smooth muscle (ASM) contractile function in asthmatic rats, and uncover the possible involvement of interleukin 4 (IL-4) and the store-operated Ca²⁺ entry (SOCE) pathway.

Methods: In this study, chicken ovalbumin was used to induce asthma in male Sprague-Dawley rats. The exercise group received moderate-intensity aerobic exercise training for 4 weeks. IL-4 concentrations in bronchoalveolar lavage fluid (BALF) samples were evaluated by enzyme linked immunosorbent assay. The contractile function of the ASM was investigated using tracheal ring tension experiments and intracellular Ca²⁺ imaging techniques. Western blot analysis was used to evaluate expression levels of calcium-release activated calcium (CRAC) channel protein (Orai) and stromal interaction molecule 1 (STIM1) in ASM.

Results: Our data showed that the carbachol-stimulated, SOCE-mediated contraction of rat ASM was significantly increased in asthmatic rats, which could be abolished by exercise. Pharmacological studies revealed that GSK5498A and BTP-2, selective blockers of CRAC channels significantly inhibited SOCE-induced ASM contraction. In addition, exercise inhibited the up-regulation of IL-4 in BALF as well as STIM1 and Orai expression in the ASM of asthmatic rats. In line with these observations, we demonstrated that pretreatment of the ASM with IL-4 up-regulated the expression level of STIM1, Orai1 and Orai2, thereby promoting SOCE-mediated ASM contraction.

Conclusions: The data in this study reveal that aerobic exercise may improve the ASM contractile function in asthmatic rats by inhibiting IL-4 secretion and by down-regulating the expression of STIM1, Orai1 and Orai2, thus decreasing excessive SOCE-mediated ASM contraction in asthmatic rats.

The worldwide prevalence of allergic disease is rising as a result of complex gene-environment interactions that shape the immune system and host response. Climate change and loss of biodiversity are existential threats to humans, animals, plants, and ecosystems. While there is significant progress in the development of targeted therapeutic options to treat allergies and asthma, these approaches are inadequate to meet the challenges faced by climate change. The exposomic approach is needed with the recognition of the bidirectional effect between human beings and the environment. All stakeholders need to work together toward mitigating the effects of climate change and promoting a One Health concept in order to decrease the burden of asthma and allergy and to improve immune health. Healthcare professionals should strive to incorporate One Health counseling, environmental health precepts, and advocacy into their practice.

Extracellular vesicles (EVs) are an end product released from almost all living cells such as eukaryotic cells and bacteria. These membrane vesicles containing proteins, lipids, and nucleic acids are mainly involved in intracellular communications through the transfer of their components from donor to acceptor cells. Moreover, EVs have been implicated in many functions in response to environmental changes, contributing to health and disease; bacterial EVs depending on their specific parental bacterium have diverse effects on immune responses to play a beneficial or pathogenic role in patients with various allergic and immunologic diseases. As bacterial EVs are a completely new area of investigation in this field, we highlight our current understanding of bacterial EVs and discuss their diagnostic and therapeutic potentials (as immunomodulators) for targeting asthma and atopic dermatitis.

Purpose: Vitamin D (VitD) is an immunomodulatory molecule capable of alleviating allergic symptoms. However, the effectiveness of allergen-specific immunotherapy (AIT) is not commonly evidenced in the early build-up phase. The aim of the study was to determine the potential of VitD supplementation in this treatment phase.

Methods: Thirty-four house dust mite (HDM)-allergic adult patients treated with subcutaneous AIT were randomized to receive VitD2 60,000 IU/week or placebo for 10 weeks and followed up for 10 weeks. The primary endpoints were the symptom-medication score (SMS) and the treatment response rate. The secondary endpoints were eosinophil count and levels of plasma IL-10, Der p 2-specific IgG4, and dysfunctional regulatory T (CRTH2⁺ Treg) cells.

Results: Of 34 patients, 15 in each group completed the study. Patients with VitD deficiency receiving a VitD supplement showed significantly lower mean change SMS than the placebo group in weeks 10 (mean difference -54.54%, P = 0.007) and 20 (mean difference -42.69%, P = 0.04). The percentage of treatment responders reached 78% and 50% in the VitD and placebo groups, respectively, and the effect remained in week 20 (89% and 60%). No significant difference was observed for the tested immunological read-outs, with the exception of the frequency of CRTH2⁺ Treg cells, which was remarkably reduced in the VitD-treated patients. Moreover, improvement in SMS was correlated to the number of CRTH2⁺ Treg cells. Our in vitro experiment indicated that VitD downregulated activation markers, whereas it improved the function of CRTH2⁺ Treg cells.

Conclusions: VitD supplementation in the build-up phase of AIT could relieve symptoms and decrease Treg cell dysfunction, especially in patients with VitD deficiency.