The characteristics in AERD are severe adult-onset asthma, eosinophilic rhinosinusitis with nasal polyposis, and CysLT overproduction. The cause of AERD have remained unclear, however the decrease in ...the production of PGE2 caused by the reduction in COX-2 activity is considered to main pathological mechanism of AERD. The mast cell activation and the interaction between platelets and granulocytes are lead to the CysLT overproduction and severe eosinophilic inflammation. The ongoing activation of mast cells is important key pathogenesis in not only stable AERD but exacerbated AERD by aspirin and NSAIDs. In recent years, type 2 inflammation caused by ILC2 activation in patients with AERD have been attracting attention. Omalizumab is effective option for AERD via suppression of mast cell activation and CysLT overproduction. Dupilumab improves sinus symptoms especially in patients with AERD. In near future, anti-platelet drug, CRTH2 antagonist, and anti-TSLP antibody may be useful candidates of therapeutic options in patients with AERD.
Biologics targeting the molecules associated with type 2 inflammation have significantly improved the outcomes of patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps ...(CRSwNP). Chronic eosinophilic airway/lung diseases including chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic bronchitis, and eosinophilic granulomatosis with polyangiitis share clinical features with eosinophilic asthma and CRPwNP, which are mostly adult-onset and may develop simultaneously or consecutively. These eosinophilic airway/lung diseases respond well to initial treatment with systemic corticosteroids, but often recur when the corticosteroids are tapered. The management of these “refractory” cases is an unmet need for clinicians. We first reviewed the standard treatments for these chronic eosinophilic airway/lung diseases, followed by the definition and prevalence of refractory diseases and the role of biologics in their management. The available evidence varies from case reports and case series to randomized control trials, depending on the type of disease; however, these studies provide not only a direction for clinical practice, but also insights into the pathophysiology of each disease. Physicians should discuss the efficacy and costs of biologics in patients with refractory eosinophilic airway/lung diseases to minimize not only the current symptoms, but future risks as well.
•Deep metric learning can be used to classify otitis media in otoscopy images.•Manual classification is observer dependent and suffers from variable accuracy.•Triplet loss captures the variation of ...an unbalanced data very well.•Using triplet loss, a high accuracy of 85% was achieved.•Presence of ear wax and blurry images pose classification challenges.
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In this study, we propose an automatic diagnostic algorithm for detecting otitis media based on otoscopy images of the tympanic membrane. A total of 1336 images were assessed by a medical specialist into three diagnostic groups: acute otitis media, otitis media with effusion, and no effusion. To provide proper treatment and care and limit the use of unnecessary antibiotics, it is crucial to correctly detect tympanic membrane abnormalities, and to distinguish between acute otitis media and otitis media with effusion. The proposed approach for this classification task is based on deep metric learning, and this study compares the performance of different distance-based metric loss functions. Contrastive loss, triplet loss and multi-class N-pair loss are employed, and compared with the performance of standard cross-entropy and class-weighted cross-entropy classification networks. Triplet loss achieves high precision on a highly imbalanced data set, and the deep metric methods provide useful insight into the decision making of a neural network. The results are comparable to the best clinical experts and paves the way for more accurate and operator-independent diagnosis of otitis media.
The presence of IgG antibodies (Abs) to Aspergillus fumigatus (Af) is a crucial diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). Although precipitation is traditionally used ...to document IgG Abs, anti-Af serum IgG levels can also be measured by enzyme immunoassay (EIA). However, there are insufficient data on the optimal cut-offs to assess diagnostic performance of the EIA method. This study aimed to determine cut-off levels of IgG binding crude Af extracts or recombinant Asp f 1 (by ImmunoCAP®) and to compare their efficacy for ABPA diagnosis with Af-precipitating Abs.
The age distribution of levels of IgG to crude extracts of Af (Af-IgG) and recombinant Asp f 1 (Asp f 1-IgG) was established using sera from 694 healthy controls (HC). Receiver operating characteristic analysis for Af-IgG and Asp f 1-IgG levels for the purpose of ABPA diagnosis was performed in 306 Af-sensitized asthma patients (including 49 ABPA), and cut-offs were determined.
An age-dependent decline in the levels of Af-IgG was observed in HC. Thus, cut-offs for Af-IgG levels were determined separately by age as 60 mg/L for patients aged <55 years, and 45 mg/L for those aged ≥55 years. For Asp f 1-IgG, 6.6 mg/L was set as the cut-off regardless of age. Although such IgG testing by EIA allowed a sufficiently good diagnostic performance, Af-precipitating Abs had better diagnostic applicability for ABPA.
We determined cut-offs for Af-IgG and Asp f 1-IgG measured by EIA, which can be useful in clinical settings where precipitating Abs are unavailable.
Several cross-sectional studies have suggested an association between obesity and asthma. However, few studies have investigated this relationship longitudinally, especially in middle-aged subjects. ...Although metabolic syndrome is a well-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial.
From 2008, specific health checkups for metabolic syndrome have been conducted throughout Japan. To seek relationships of obesity and metabolic syndrome with late-onset asthma in Japan, we analyzed data collected from health insurance claims and specific health checkups for metabolic syndrome at three large health insurance societies. Among subjects aged 40–64 years (n = 9888), multivariate logistic regression analyses were performed to investigate the relationships of obesity and metabolic syndrome in fiscal year 2012 (from April 2012 to March 2013) with the incidence of late-onset asthma in the following two years (from April 2013 to March 2015).
In women, BMI 25–29.9 kg/m2 or ≥30 kg/m2, waist circumference ≥90 cm, and waist-to-height ratio ≥0.5 were shown to be significant risk factors for asthma, with adjusted odds ratios (95% CI) of 1.92 (1.35–2.75), 2.24 (1.23–4.09), 1.89 (1.30–2.75), and 1.53 (1.15–2.03), respectively. Significance was retained even after adjustment for metabolic syndrome, and there were no significant relationships between metabolic syndrome itself and the incidence of asthma in men or women.
Only the obesity measures, not metabolic syndrome, were shown to be significant risk factors for the incidence of late-onset asthma but only in middle-aged Japanese women, and not in men.
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Dear Editor, Gibberellin-regulated protein (GRP), present in various fruits including peach, Japanese apricot, and orange, was recently identified as a novel food allergen that may cause severe ...allergic reactions. Concurrently, GRPs have been reported to be present in Cupressaceae pollen including Mediterranean cypress (Cupressus sempervirens) and Japanese cedar (Cryptomeria japonica) pollen. Thus, whether Cupressaceae-pollen-GRP is a primary sensitizer in patients with fruit-GRP allergy is matter of debate. The highest frequency of allergy to fruit-GRP was reported from Cupressaceae pollen-dispersal countries including France and Japan, whereas few cases have been reported from Spain and Italy. Furthermore, the frequencies of sensitization to peach GRP have been associated positively with the level of cypress pollen exposure. These findings support the idea that the GRP protein in Cupressaceae pollen acts as a primary sensitizer, resulting in cross-reactivity to fruit-GRP.
Airway epithelium-derived cytokines are critical to provoke and perpetuate type 2 inflammation in asthma. Yet it is poorly understood how this epithelial cell-driven inflammatory response is ...negatively regulated. We previously reported that Axl receptor tyrosine kinase was expressed by basal cells in the airway epithelium and had a role in defining their stem cell identity. However, whether and how Axl regulates airway type 2 inflammation remains unknown.
We performed immunofluorescence staining to compare Axl expression in airway epithelium between non-asthmatic subjects, mild-moderate asthma and severe asthma. We confirmed this result by interrogating public databases of global gene expression in endobronchial biopsies. We then quantified eosinophil numbers infiltrating into the trachea of wild-type or Axl-knockout mice that were intranasally treated with house dust mite extracts (HDM). Cell-based assays using siRNA targeting Axl were further performed to identify molecules involved in Axl-mediated regulation of inflammation.
Histological assessments and transcriptome analyses revealed decreases in protein and mRNA of Axl in airway basal cells of severe asthmatics. This reduction of Axl expression was correlated with infiltration of eosinophils and mast cells in severe asthmatics. Eosinophil infiltration was more evident in the trachea of Axl-knockout mice in response to repetitive HDM administration. siRNA-mediated knockdown of Axl increased mRNA and protein expression of granulocyte macrophage-colony stimulating factor (GM-CSF) in human bronchial epithelial cells.
Axl kinase expressed by basal cells may suppress excessive eosinophilic inflammation via inhibition of GM-CSF in the airway. Axl reduction has clinical implications for the pathogenesis of severe asthma.
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