Allergy, Asthma & Immunology Research最新文献

Background: Asthma-bronchiectasis overlap (ABO) encompasses heterogeneous manifestations, which may predict distinct clinical outcomes. We sought to identify the clinical phenotypes of ABO and compare them to asthma alone or bronchiectasis alone.

Methods: In this retrospective cohort study, we extracted electronic medical records from 292 inpatients with ABO, 901 inpatients with asthma alone, and 1,192 inpatients with bronchiectasis alone who were hospitalized between 2015 and 2020. We phenotyped ABO using 2-step unsupervised clustering analysis by using an independent cohort (n = 76).

Results: Compared to asthma or bronchiectasis alone, ABO exhibited greater disease severity and worse clinical outcomes. We identified 3 ABO phenotypes: asthma-dominant ABO (ABO-A, n = 100) with more prominent asthma symptoms; bronchiectasis-dominant ABO (ABO-B, n = 89) with more pronounced features of bronchiectasis; and co-existence of asthma and severe bronchiectasis (ABO-S, n = 103) with worse clinical outcomes. Compared to ABO-B, both ABO-A and ABO-S were associated with significantly higher blood neutrophil ratios (55.8% vs. 59.1% vs. 64.4%, P < 0.001), poorer lung function (FEV1% predicted: 79.1% vs. 67.5% vs. 50.1%, P < 0.001), longer hospital stay (6.0 vs. 7.0 vs. 7.0 days, P = 0.004), and higher risks of hospitalization within the next 2 years (ABO-A: hazards ratio [HR], 3.76, 95% confidence interval [CI], 1.12-12.62, P = 0.032; ABO-S: HR, 4.05, 95% CI, 1.14-14.36, P = 0.031).

Conclusions: The radiologic severity of bronchiectasis and the use of systemic corticosteroids can identify the clinical phenotypes of ABO. The heterogeneity of clinical manifestations may help formulate personalized management strategies and predict the prognosis of ABO.

Purpose: We present a convenient and safe allergen-specific immunotherapy using injectable hyaluronic acid (HA) hydrogel containing house dust mite (HDM) crosslinked via visible-light-induced thiol-ene reaction.

Methods: We developed 2 types of HDM-containing HA hydrogels, namely thiolated HA (SH-HA) + methacrylated HA (MA-HA) (Gel-1) and 4-arm poly (ethylene glycol) (PEG)-SH + MA-HA (Gel-2). The immunotherapeutic effect of the hydrogels was tested using a murine model of allergic rhinitis. Sensitized mice received 3 subcutaneous injections of the HDM extract (subcutaneous immunotherapy [SCIT] group) or phosphate buffer saline (negative and positive control) at 2-day intervals. Mice in the HA hydrogel immunotherapy groups received one subcutaneous injection of each HA hydrogel precursor solution that formed hydrogel by transmitting blue light through the skin. All except the negative control received HDM extract intranasally for 5 days. Nasal symptoms, ear swelling, eosinophil count, antibody levels, and histopathology of the nasal mucosa were analyzed.

Results: All HDM-containing immunotherapy groups exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage compared to the positive control group. Eosinophils, mast cells, and goblet cells in the nasal mucosa decreased in all treatment groups compared to the positive control group. The serum levels of HDM-specific immunoglobulin G (IgG)1 increased in all treatment groups; however, IgG2a levels increased only in the SCIT and Gel-2 groups. Interleukin (IL)-4, 13, and 17 decreased in all treatment groups compared to those in the positive control group, whereas IL-10 level increased only in the SCIT and Gel-2 groups. SCIT and Gel-2 treatment showed similar capability to induce regulatory T cells.

Conclusions: Injectable HA hydrogel containing HDM reduced allergic symptoms and induced tolerance in a murine model of allergic rhinitis.

Despite the importance of comorbid ischemic heart disease (IHD) in the prognosis of asthma, the long-term impact of coronavirus disease 2019 (COVID-19) on IHD in adults with asthma remains unclear. This study investigated the long-term effects of COVID-19 on the risk of IHD in individuals with asthma, particularly regarding COVID-19 severity. Using the Korean National Health Insurance Service claims database, we identified individuals with asthma who had recovered from COVID-19 between October 8, 2020, and December 31, 2021 (n = 8,011) and 1:1 propensity score-matched controls (n = 8,011). The incidence and risk of IHD were compared between the two groups. Overall, during a median follow-up of 95 days (interquartile range, 34-213 days; range, 1-448 days), which includes a median of 14 lag days, the COVID-19 cohort did not show a higher risk of IHD (hazard ratio [HR], 2.11; 95% confidence interval [CI], 0.99-4.48) compared to matched controls. However, when the severity of COVID-19 was considered, the severe COVID-19 cohort exhibited a higher risk of IHD (HR, 4.89; 95% CI, 1.86-12.84) than matched controls; in contrast, the non-severe COVID-19 cohort showed no significantly increased risk of IHD (HR, 1.64; 95% CI, 0.73-3.70). Severe COVID-19 is associated with an increased long-term risk of IHD in adults with asthma, emphasizing the importance of cardiovascular events monitoring to improve asthma treatment outcomes in the era of COVID-19.

Chronic rhinosinusitis (CRS) is a prevalent airway disease, leading to health, social, and economic burdens, and substantially impairs quality of life. As CRS is heterogeneous and contains diverse pathogenesis, treatment outcomes and prognosis vary from curative to intractable. Inflammatory endotypes of CRS are divided into 3 types-type 1, type 2 and type 3-based on cytokines promoted. Tissue/blood eosinophilia seems to be the most reliable and feasible biomarker for type 2 CRS in clinical settings, although the cutoff level of eosinophilia remains to be elucidated. In East Asia, the predominant pathogenesis has changed from neutrophilic type 3 inflammation to eosinophilic type 2 inflammation over the past decades. The treatment strategy for CRS has also evolved from classical phenotype-based "reliever-controller" treatment to endotype-based "treatable traits" treatment. "Treatable traits" treatment is a personalized approach for the management of airway disease with complex and heterogeneous conditions. In CRS, traits can be grouped into sinonasal, extra-nasal and risk factor/behavioral domains. Type 2 CRS is one of the sinonasal traits, and biologics targeting immunoglobulin E, interleukin (IL)-5 and its receptor, IL-4/IL-13 receptor (IL-4/IL-13R) and thymic stromal lymphopoietin are the corresponding treatments for this trait. Proper use of these biologics can achieve high efficacy with patient satisfaction, leading to clinical remission. However, some cases show marked hypereosinophilia after the reduction or discontinuation of systemic corticosteroid or the switching of biologics from anti-IL-5/IL-5R to anti-IL-4Rα monoclonal antibody. More precise research on CRS targeting endotype, genotype, regiotype and theratype is needed to address the unmet needs and refine the "treatable traits" treatment of CRS.

This corrects the article on p. 863 in vol. 13, PMID: 34734505.

Angiogenesis is an important event in the development of allergic inflammation as well as in the pathophysiology of tissue remodeling in asthma. Increased angiogenesis is a well-documented feature of airway remodeling in asthma. Angiogenesis refers to the formation of new blood vessels from pre-existing endothelium. Angiogenesis can be initiated by endogenous angiogenic factors released from mesenchymal cells or inflammatory cells. Under physiological conditions, angiogenesis is controlled by an equilibrium between pro-endogenous and anti-endogenous angiogenic factors released from the extracellular matrix to become bioavailable. The presence of increased size and number of bronchial blood vessels indicates that angiogenesis plays a crucial role in tissue growth and remodeling in asthma. However, the diagnostic significance of circulating angiogenic factors in asthma remains unclear. This review summarizes the role of angiogenesis in airway remodeling in asthma, and the potential diagnostic implications of circulating angiogenetic factors.

Shellfish and fish are common causes of food allergy (FA) in Asia, with significant prevalence rates reported across various countries. This study aimed to identify the diagnostic decision points (DDPs) for shrimp, crab, and cod allergies in Korean children. We enrolled participants aged 18 years or younger with suspected shrimp, crab, or cod allergies through a retrospective review of medical records from a nationwide 14-center study between January 2018 and March 2022. FA was diagnosed using an open oral food challenge or a reproducible and convincing history with positive serum specific immunoglobulin E (sIgE) levels. The sIgE cut-off values for shrimp, crab, and cod were determined by analyzing receiver operating characteristic curves. Out of 266 children, 90 (33.8%) were confirmed to have a shrimp allergy. Crab allergies were found in 37 (39.8%) of 93 children. Of 66 children, 15 (22.7%) were found to be allergic to cod. The optimal sIgE cut-off values based on the largest area under the curve were 1.43, 3.25, and 2.05 kU/L for shrimp, crab, and cod, respectively. Levels of sIgE with more than 90% positive predictive value (PPV) were 33.8, 47.5, and 29.9 kU/L for shrimp, crab, and cod, respectively. Levels of sIgE with greater than 90% negative predictive value (NPV) were 0.36, 0.04, and 3.93 kU/L for shrimp, crab, and cod, respectively. Our results suggest that DDPs of sIgE levels with high PPV and NPV can be used to diagnose shrimp, crab, and cod allergies in Korean children.

Purpose: Neutrophilic asthma (NA) is associated with more severe symptoms and poor responsiveness to inhaled corticosteroid therapy. Macrophages are the most abundant immune cells in the airway, but the role of macrophages in NA pathogenesis has not been fully studied. We hypothesized that dysregulation of peroxisome metabolism in macrophages may drive NA.

Methods: We retrieved microarray datasets from the GEO Gene Expression Omnibus database by using induced sputum samples from eosinophilic and neutrophilic asthma patients as well as healthy controls. We identified key molecules in NA and validated the expression of the key genes in our cohort of asthma patients using quantitative polymerase chain reaction (PCR). Furthermore, immunofluorescence staining was performed to detect the expression and localization of the key molecule in bronchoalveolar lavage (BAL) cells from asthma patients and the murine model of neutrophilia-dominant allergic airway inflammation. The expression of the key molecule was also examined in mouse bone marrow-derived macrophages (BMDMs) by quantitative PCR and western blotting.

Results: Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), sterol carrier protein 2, and peroxisomal biogenesis factor 14 were identified as the key molecules and were downregulated in patients with NA or severe asthma. The peroxisomal fatty acid metabolism pathway was significantly downregulated in NA. In our cohort of asthma patients, the expression of EHHADH, a key enzyme of the peroxisomal fatty acid beta-oxidation, was significantly decreased in non-eosinophilic asthma patients and positively correlated with airflow limitation. EHHADH was primarily expressed in macrophages in BAL cells. EHHADH was downregulated in lipopolysaccharide (LPS)-induced M1-like macrophages in mouse BMDMs. Fenofibrate, an agonist of the peroxisome pathway, significantly inhibits LPS-induced macrophage M1 polarization.

Conclusions: EHHADH expression and the peroxisome metabolism pathway are downregulated in macrophages in patients with NA. This downregulation may contribute to macrophage M1 polarization and neutrophilic airway inflammation in asthma.