Phospholipase A₂s (PLA₂s) are a group of enzymes that hydrolyze the sn-2 position of phospholipids to release (typically unsaturated) fatty acids and lysophospholipids, which serve as precursors for a variety of bioactive lipid mediators. Among the PLA₂ superfamily, secreted PLA₂ (sPLA₂) enzymes comprise the largest subfamily that includes 11 isoforms with a conserved His–Asp catalytic dyad. Individual sPLA₂ enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. Recent studies using transgenic and knockout mice for individual sPLA₂ isofoms have revealed their involvement in various pathophysiological events. Here, we overview the current state of knowledge about sPLA₂s, specifically their roles in mast cells (MCs) in the context of allergology. In particular, we highlight group III sPLA₂ (PLA2G3) as an "anaphylactic sPLA₂" that promotes MC maturation and thereby anaphylaxis through a previously unrecognized lipid-orchestrated circuit.

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Prostanoids, which include prostaglandin and thromboxane, are metabolites of arachidonic acid released in various pathophysiological conditions. They induce a range of actions mediated through their respective receptors expressed on target cells. It has been demonstrated that each prostanoid receptor has multiple functions and that the effect of receptor stimulation can vary depending on context; this sometimes results in opposing effects, such as simultaneous excitatory and inhibitory outcomes. The balance between the production of each prostanoid and the expression of its receptors has been shown to be important for maintaining homeostasis but also involved in the development of various pathological conditions such as allergy. Here, we review the recent findings on the roles of prostanoids in allergy, especially focusing on atopic dermatitis and asthma.

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Leukotrienes (LTs), both LTB₄ and the cysteinyl LTs (CysLTs) LTC₄, LTD₄ and LTE₄, are implicated in a wide variety of inflammatory disorders. These lipid mediators are generated from arachidonic acid via multistep enzymatic reactions through which arachidonic acid is liberated from membrane phospholipids through the action of phospholipase A₂. LTB₄ and CysLTs exert their biological effects by binding to cognate receptors, which belong to the G protein-coupled receptor superfamily. LTB₄ is widely considered to be a potent chemoattractant for most subsets of leukocytes, whereas CysLTs are potent bronchoconstrictors that have effects on airway remodeling. LTs play a central role in the pathogenesis of asthma and many other inflammatory diseases. This review will provide an update on the synthesis, biological function, and relevance of LTs to the pathobiology of allergic diseases, and examine the current and future therapeutic prospects of LT modifiers.

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Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found naturally in fish oil and are commonly thought to be anti-inflammatory nutrients, with protective effects in inflammatory diseases including asthma and allergies. The mechanisms of these effects remain mostly unknown but are of great interest for their potential therapeutic applications. Large numbers of epidemiological and observational studies investigating the effect of fish intake or omega-3 fatty acid supplementation during pregnancy, lactation, infancy, childhood, and adulthood on asthmatic and allergic outcomes have been conducted. They mostly indicate protective effects and suggest a causal relationship between decreased intake of fish oil in modernized diets and an increasing number of individuals with asthma or other allergic diseases. Specialized pro-resolving mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3 fatty acids such as EPA and DHA via several enzymatic reactions. These mediators counter-regulate airway eosinophilic inflammation and promote the resolution of inflammation in vivo. Several reports have indicated that the biosynthesis of SPM is impaired, especially in severe asthma, which suggests that chronic inflammation in the lung might result from a resolution defect. This article focuses on the beneficial aspects of omega-3 fatty acids and offers recent insights into their bioactive metabolites including resolvins and protectins.

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Background: There are scarce data about the prevalence of Hymenoptera venom allergy in the general population. The aim of this study was to determine the prevalence of Hymenoptera venom allergy in the general adult population of Istanbul.
Methods: A total of 17,064 randomly selected telephone numbers were contacted and 11,816 (69.25%) individuals who agreed to participate completed a questionnaire. Those who disclosed hypersensitivity reactions due to Hymenoptera stings in this initial survey were called again and given another questionnaire. Those who were suspected of experiencing hypersensitivity reactions to Hymenoptera stings were invited for a clinical investigation with in vivo and in vitro diagnostic tests.
Results: According to the first questionnaire, a total of 1171 (9.9%; 95% CI: 9.38–10.47%) were suspected of having a hypersensitivity to Hymenoptera stings. 51.75% (n: 606) answered the second questionnaire and 21% (n: 128) of these were still suspected of having a hypersensitivity to Hymenoptera stings (1.1%; 95% CI: 0.9–1.29%). The confirmed prevalence of hypersensitivity to Hymenoptera stings according to skin tests and in vitro sIgE levels was 0.2% (95% CI: 0.14–0.30%). Nearly all of the participants with systemic reactions were admitted to the emergency department, although only one tenth of them received adrenaline in the emergency room. 2.3% carried an adrenaline injector, whereas none of the patients received venom immunotherapy.
Conclusions: The prevalence of Hymenoptera sting reactions in our geographical region is comparable with other European studies. There is a need to increase the awareness of adrenaline in the emergency management of insect sting anaphylaxis and venom immunotherapy in the prophylaxis.

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Background: Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis.
Methods: To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin's role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ).
Results: Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, −22, or −23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells.
Conclusions: Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis.

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Background: Chronic obstructive pulmonary disease (COPD) is highly prevalent worldwide. COPD is a treatable disease and it is important to identify COPD subjects, highlighting the need for an efficient screening measure. Although the COPD screening questionnaire (COPD Population Screener, COPD-PS) was developed as a screening tool, its validity is not clear in population-based studies. This study determines the validity of the COPD-PS in the general Japanese population.
Methods: All registered residents living in the town of Hisayama aged above 40 were solicited to participate in a health check-up in 2012. All subjects aged 40–79 without physician-diagnosed asthma or lung resection were recruited, and 2357 subjects with the COPD-PS recorded and valid spirometry measurements were analyzed. Persistent airflow obstruction (AO) was defined by post-bronchodilator FEV₁/FVC < 0.7. The sensitivity and specificity of the COPD-PS score for identifying AO was assessed by logistic regression analysis.
Results: The prevalence of AO in this population was 6.5%. The overall area under the receiver operating characteristic (ROC) curve for the continuous COPD-PS score was 0.748. A cut-point of 4-points is recommended, resulting in a sensitivity of 67.1% and specificity of 72.9% with an area under the ROC curve of 0.70. The positive predictive value was 14.6% and negative predictive value was 97.0%.
Conclusions: The COPD-PS appears to be an adequate measure for large scale screening of possible airflow obstruction requiring further testing with spirometry.

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Background: This study aims to examine the immunological parameters, focusing IL-10 productivity, in prophylactic sublingual immunotherapy (SLIT) in asymptomatic subjects sensitized to Japanese cedar pollen (JCP).
Methods: This study was conducted as part of a randomized, double-blind, placebo-controlled, multiple center trial, and was performed for two consecutive pollen seasons in 2012 and 2013. The present results were based only on our institution. We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering. The SLIT group received standardized JCP extract for five months over the pollen season. We observed and judged development of the symptoms in the pollen season. The percentage of IL-10 producing CD4⁺ T (Trl) cells, B cells and monocytes were analyzed by flow cytometry. JCP specific IgE and total IgE were also measured.
Results: The ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013. In 2012, the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group. In 2013, the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group. The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group.
Conclusions: Prophylactic SLIT is effective for prevention of the development of pollinosis. Induction of IL-10 producing T cells, B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects.

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Background: Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed for the treatment of allergic rhinitis (AR). This study aimed to assess the safety, efficacy, and systemic exposure of FFNS in Japanese children with perennial AR (PAR).
Methods: In this multicentre, open-label, phase 3 study, 61 children aged 2 to <15 years were treated with FFNS 55 μg, once daily for 12 weeks. Nasal and ocular symptoms were scored by parents/guardians/patients and recorded in a patient's daily diary. In addition, rhinoscopy findings, including mucosal swelling, were scored by the investigators as an efficacy measure. As a safety measure, adverse events and clinical laboratory data were evaluated.
Results: An adverse event was reported by 67% of patients during the treatment and follow-up period, all of which were mild in intensity. The most commonly reported adverse events were nasopharyngitis and acute sinusitis (acute rhinosinusitis). There were no serious adverse events. FFNS 55 μg improved nasal symptom scores and rhinoscopy findings compared with the baseline. Ocular symptom scores were also improved compared with the baseline in FFNS 55 μg in a sub-group of patients with any ocular symptoms at baseline. FFNS 55 μg was shown to be well tolerated over the 12-week treatment period. Majority of patients receiving FFNS 55 μg had unquantifiable plasma levels of fluticasone furoate (FF).
Conclusions: Twelve-week treatment with FFNS 55 μg, once daily, is well tolerated and effective with low systemic exposure in Japanese children aged 2 to <15 years with PAR.

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Background: The consumption of cooking oils may exacerbate some allergic diseases. In the present study, the effects of naturally oxidized olive oil on immediate- and/or delayed-type allergic reactions were investigated in BALB/c mice.
Methods: Mouse models of 3 types of allergic reactions: contact hypersensitivity (CHS), active cutaneous anaphylaxis (ACA), and DNFB-induced hypersensitivity, were orally administered naturally oxidized olive oil that was obtained by keeping the oil at room temperature for more than 3 years. The effects of ultraviolet ray (UV)-irradiated olive oil and other dietary oils as well as their possible oxidation products on CHS were also investigated.
Results: Naturally oxidized olive oil had a high peroxide value (POV) and exacerbated CHS, ACA, and DNFB-induced hypersensitivity in a POV-dependent manner. UV-irradiated olive oil, corn oil, sesame oil and triolein had high POVs, but almost the same acid value (AV) and thiobarbituric acid-reactive substance (TBARS) level as fresh oils. Fresh olive oil and the representative oxidation product with a high AV or TBARS level had no effect on CHS, whereas all UV-irradiated oils and naturally oxidized olive oil exacerbated it.
Conclusions: Oxidized dietary oils that have high POVs exacerbated immediate- and/or delayed-type allergic reactions regardless of the different oil constituents or oxidation processes.

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Background: There have recently been reports suggesting that sensitization to food allergens may occur outside the intestinal tract, especially through the skin. To clarify the role of epicutaneous sensitization in food allergy, we investigated the clinical characteristics of adult patients with food allergies preceded by contact urticaria due to the same foods.
Methods: We investigated clinical characteristics of 15 patients (20–51 years of age; 5 men and 10 women), who had food allergies preceded by contact urticaria.
Results: Fourteen patients were contact urticaria due to the causative foods during occupationally cooking, whereas 1 patient during face pack. In the occupational group, causative foods included rice, wheat, fruits, vegetables, fish, shrimp and cuttlefish; in the fresh cucumber paste case the cause was cucumber. In the 15 patients, the causative foods were fresh, not processed, and were tolerated by most (9/15, 60%) after heating. Regarding to symptoms after ingestion of the causative foods, the most frequently induced symptoms was oral symptoms (14/15, 93.3%), followed by urticaria (4/15, 26.7%), abdominal symptoms (3/15, 20%). The duration between the start of jobs or face pack, and the onset of contact urticaria was from 1 month to 19 years (mean, 8.7 years). The duration between the onset of contact urticaria and the onset of food allergy was from a few weeks to 6 years (mean, 11 months). One sushi cook experienced severe anaphylactic shock after ingestion of fish. In the occupational group, 13 of 15 patients (86.7%) had atopic dermatitis or hand eczema, indicating that the impaired skin barrier might be a risk for food allergies induced by epicutaneous sensitization.
Conclusions: Epicutaneous sensitization of foods could induce food allergy under occupational cooking and skin-care treatment with foods in adults.

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Background: Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and often coexists with asthma or chronic obstructive pulmonary disease (COPD); however, it is unknown whether there are differences in the effect of GERD on these diseases. The purpose of this study was to assess the difference in the effect of GERD on cough-related quality of life and disease status in asthma and COPD in a real-world setting.
Methods: Subjects were 132 patients with overall controlled asthma and 102 patients with stable COPD. They completed the frequency scale for symptoms of GERD (FSSG), a validated Japanese questionnaire for GERD, the Leicester Cough Questionnaire (LCQ), and the Asthma Control Test (ACT) or COPD assessment test (CAT) questionnaires.
Results: We found that 29 (22.0%) patients with asthma and 22 (21.6%) patients with COPD had GERD. There was no difference in the FSSG scale between the diseases. The patients with GERD, regardless of having asthma or COPD, had lower LCQ scores affecting all health domains and lower ACT or higher CAT scores than those without GERD. Overall, the patients with COPD had lower LCQ scores regardless of the presence or absence of GERD. The FSSG scale was negatively correlated with the LCQ total score in asthma and in COPD. In contrast, the FSSG scale was positively correlated with the CAT score but not with the ACT score.
Conclusions: Patients with GERD had impaired cough-related quality of life, poor asthma control or more symptoms and impacts of COPD.

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Background: Reliable assessment of not only symptoms but also lung function is essential in asthma management. We developed a new technology for analyzing lung sounds and assessed its clinical usefulness in asthmatic children.
Methods: Forty-four children underwent lung sound recording with simultaneous airflow measurement using a sensor on the upper right anterior chest. We calculated a sound parameter index from the amplitude of inspiratory lung sounds at 700 Hz (ic700). ic700 were compared depending on flow and body size. In addition, 184 asthmatic children and 16 non-asthmatic children underwent lung sound analysis and lung function test in an asymptomatic state. In the asthma group, 135 children received treatment continually. The untreated asthma group included 28 children who had never received treatment continually and 21 children who had not been treated for at least 1 year. The asthmatic children were divided into four classes according to asthma severity. ic700 were compared depending on spirometric parameters and asthma severity classification.
Results: The influences of flow and body size were negligible for ic700. ic700 correlated with FEV₁%, MMF and FEF50 (r = −0.436, −0.339 and −0.302, respectively). There was a significant difference of ic700 between asthmatic and non-asthmatic children (p < 0.001), and ic700 correlated with the classification of asthma severity (p < 0.001). The ic700 scores of the severe group were higher than those of the intermittent group and non-asthmatic children.
Conclusions: It was possible to evaluate airway dysfunction of asthma using ic700, which was calculated non-invasively by analyzing lung sounds alone, without measuring body size and airflow.

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Background: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy.
Methods: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14).
Results: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points.
Conclusions: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.

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