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Growing Up in Singapore with allergies – Lessons learnt from the GUSTO & S-PRESTO cohorts 在新加坡因过敏而长大-GUSTO和S-PRESTO团队的经验教训。
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.09.003
Noor H.A. Suaini , Hugo Van Bever , Elizabeth Huiwen Tham

Healthcare systems across the world face major challenges due to allergic diseases, known to affect people of all ages. In Singapore, two prominent cohort studies, Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO), have made notable advancements to our knowledge and understanding of allergic diseases. These cohorts, which comprised of healthy mother-infant dyads recruited from the healthy Singapore population, have shed light on the complex connections between factors influencing health in early life, preconception and pregnancy, on the pathogenesis of allergic disorders in offspring.

GUSTO highlighted significant risk factors in antenatal and early life, such as maternal diet, health and lifestyle choices, as well as infant environmental influences, that contributed to the risk of allergic diseases in the Asian Singaporean population. It also identified differential patterns of allergic disease in comparison to other populations, particularly the role of the microbiome in predicting atopic outcomes. Meanwhile, S-PRESTO further explores the long-term maternal and child outcomes associated with preconception health. Findings seem to suggest that prevention of offspring allergic conditions can be achieved through optimizing maternal health and lifestyle choices before conception.

Both studies underscore the significance of early life interventions, preconception health, and personalized approaches to effectively manage and prevent allergies. By leveraging the insights and promising findings from GUSTO and S-PRESTO, future work can drive development of preventative strategies and personalized interventions to reduce burden of allergic diseases in the Singapore population.

由于过敏性疾病,世界各地的医疗保健系统都面临着重大挑战,众所周知,过敏性疾病会影响所有年龄段的人。在新加坡,两项著名的队列研究,即《在新加坡成长走向健康结果》(GUSTO)和《新加坡长期母婴结果预受孕研究》(S-PRESTO),在我们对过敏性疾病的认识和理解方面取得了显著进步。这些队列由从健康的新加坡人群中招募的健康母婴二人组组成,揭示了影响早期健康、孕前和怀孕的因素之间的复杂联系,以及后代过敏性疾病的发病机制。GUSTO强调了产前和早期生活中的重要风险因素,如母亲的饮食、健康和生活方式选择,以及婴儿的环境影响,这些因素导致了新加坡亚裔人群患过敏性疾病的风险。它还确定了与其他人群相比过敏性疾病的不同模式,特别是微生物组在预测特应性结果中的作用。同时,S-PRESTO进一步探讨了与先入为主健康相关的长期母婴结果。研究结果似乎表明,通过在受孕前优化母亲的健康和生活方式选择,可以预防后代过敏。这两项研究都强调了早期生活干预、先入为主的健康和个性化方法对有效管理和预防过敏的重要性。通过利用GUSTO和S-PRESTO的见解和有希望的发现,未来的工作可以推动预防策略和个性化干预措施的发展,以减轻新加坡人群中过敏性疾病的负担。
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引用次数: 0
Eosinophil extracellular trap formation in the giant papillae of atopic keratoconjunctivitis and vernal keratoconjunctivitis 特应性角结膜炎和春季角结膜炎大乳头中嗜酸性粒细胞外陷阱的形成。
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.10.002
Miki Onoue , Akiko Saga , Keisuke Adachi , Yosuke Asada , Toshiaki Hirakata , Satoshi Iwamoto , Shigeharu Ueki , Nobuyuki Ebihara , Akira Matsuda
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引用次数: 0
Evaluation of elevated plasma fatty acids as relevant factors for adult-onset asthma: The Nagahama Study 评估血浆脂肪酸升高与成人哮喘的相关因素:长滨研究
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.04.005
Noriyuki Tashima , Hisako Matsumoto , Kenta Nishi , Satoru Terada , Mariko Kogo , Natsuko Nomura , Chie Morimoto , Hironobu Sunadome , Tadao Nagasaki , Tsuyoshi Oguma , Yoshinari Nakatsuka , Kimihiko Murase , Takahisa Kawaguchi , Yasuharu Tabara , Kazuo Chin , Kazuhiro Sonomura , Fumihiko Matsuda , Toyohiro Hirai

Background

Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma.

Methods

This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA).

Results

In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males.

Conclusions

Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.

背景肥胖和体重指数(BMI)升高是成人哮喘发病的已知风险因素。肥胖患者的血清游离脂肪酸(FFA)和其他血脂水平普遍升高,可能与哮喘的发病有关。然而,这在很大程度上仍是个未知数。本研究旨在阐明血浆脂肪酸与新发哮喘之间的关系。我们在基线和 5 年后的随访中进行了自我报告问卷调查、肺功能测试和血液测试。随访时,我们使用气相色谱-质谱法测量了血浆脂肪酸。随访时还进行了身体成分分析。采用目标偏最小二乘判别分析(PLS-DA)等多方面方法评估了脂肪酸与新发哮喘之间的关联。在多变量分析中,较高水平的脂肪酸、棕榈油酸或油酸与新发哮喘显著相关,与其他干扰因素无关。高体脂百分比本身并非相关因素,但与血浆棕榈油酸对新发哮喘的影响呈正交互作用。结论血浆脂肪酸(尤其是棕榈油酸)水平升高可能是导致新发哮喘的一个相关因素。
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引用次数: 1
Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics 治疗前循环 MAIT 细胞、中性粒细胞和包膜蛋白可预测哮喘患者接受 1 年美泊珠单抗治疗后的实际反应
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.06.001
Hitoshi Sasano , Norihiro Harada , Sonoko Harada , Tomohito Takeshige , Yuuki Sandhu , Yuki Tanabe , Ayako Ishimori , Kei Matsuno , Tetsutaro Nagaoka , Jun Ito , Asako Chiba , Hisaya Akiba , Ryo Atsuta , Kenji Izuhara , Sachiko Miyake , Kazuhisa Takahashi

Background

Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical responsiveness to mepolizumab after 1-year treatment.

Methods

Twenty-seven patients with severe asthma were treated with mepolizumab for one year. Asthma control test scores, pulmonary function tests, fractional exhaled nitric oxide levels, and blood samples were evaluated. Additionally, we explored the role of CD69-positive mucosal-associated invariant T (MAIT) cells as a candidate biomarker for predicting treatment effectiveness by evaluating an OVA-induced asthma murine model using MR1 knockout mice, where MAIT cells were absent.

Results

The frequencies of CD69-positive group 1 innate lymphoid cells, group 3 innate lymphoid cells, natural killer cells, and MAIT cells decreased after mepolizumab treatment. The frequency of CD69-positive MAIT cells and neutrophils was lower and serum periostin levels were higher in responders than in non-responders. In the OVA-induced asthma murine model, CD69-positive MAIT cell count in the whole mouse lung was significantly higher than that in the control mice. Moreover, OVA-induced eosinophilic airway inflammation was exacerbated in the MAIT cell-deficient MR1 knockout mice.

Conclusions

This study shows that circulating CD69-positive MAIT cells, neutrophils, and serum periostin might predict the real-world response after 1-year mepolizumab treatment. Furthermore, MAIT cells potentially have a protective role against type 2 airway inflammation.

背景美妥珠单抗治疗可改善严重嗜酸性粒细胞性哮喘患者的症状控制和生活质量,并减少病情恶化。然而,必须确定预测疗效的生物标志物,以便用于精准医疗。在此,我们阐明了治疗前后各种参数的动态变化,以及治疗一年后预测对美泊珠单抗临床反应性的患者特征。我们对哮喘控制测试评分、肺功能测试、呼出一氧化氮分数水平和血液样本进行了评估。此外,我们还通过评估 OVA 诱导的哮喘小鼠模型,使用 MR1 基因敲除小鼠(MR1 基因敲除小鼠不存在 MAIT 细胞),探讨了 CD69 阳性粘膜相关不变 T 细胞(MAIT)作为预测治疗效果的候选生物标记物的作用。与非应答者相比,应答者 CD69 阳性 MAIT 细胞和中性粒细胞的频率较低,血清包膜生长因子水平较高。在 OVA 诱导的哮喘小鼠模型中,小鼠全肺中 CD69 阳性 MAIT 细胞数明显高于对照组小鼠。此外,在 MAIT 细胞缺陷的 MR1 基因敲除小鼠中,OVA 诱导的嗜酸性粒细胞气道炎症会加重。结论这项研究表明,循环中 CD69 阳性的 MAIT 细胞、中性粒细胞和血清包膜生长因子可能会预测美妥珠单抗治疗 1 年后的真实世界反应。此外,MAIT 细胞可能对 2 型气道炎症具有保护作用。
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引用次数: 1
Exacerbation rates in Japanese patients with obstructive lung disease: A subanalysis of the prospective, observational NOVELTY study 日本阻塞性肺病患者的病情恶化率:前瞻性观察研究 NOVELTY 的子分析
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.08.003
Tomotaka Kawayama , Kenichi Takahashi , Toshikazu Ikeda , Kenya Fukui , Naoyuki Makita , Naoki Tashiro , Junpei Saito , Toshihiro Shirai , Hiromasa Inoue

Background

Although clinical trials including asthma and COPD patients have revealed much about exacerbation frequencies, most studies are limited in that they recruited patients only with a clear diagnosis of one disease or the other, based on conventional diagnostic criteria, which may exclude many real-world patients with mixed symptoms.

Methods

NOVELTY is a global prospective observational study of patients with asthma and/or COPD from real-world practice. In this subanalysis, we compared patient characteristics of obstructive pulmonary diseases between the Japanese population (n = 820) and the overall population excluding Japanese patients (n = 10,406).

Results

The Japanese population had fewer exacerbations than the overall population across most of the physician-assessed disease severities and all diagnoses. The difference in exacerbation frequencies was more prominent in patients with COPD and asthma + COPD. The Japanese population was older, had higher former smoking rates, lower BMI, fewer respiratory symptoms, and better health-related quality of life compared with the overall population across all diagnoses.

Conclusions

We clarified differences in patient characteristics among patients with asthma and/or COPD in Japan compared with non-Japanese patients. Importantly, we found that Japanese patients with asthma and/or COPD had significantly fewer exacerbations compared with patients overall. The results from our study may contribute to the development of precision medicine and guidelines specific to Japan.

背景虽然包括哮喘和慢性阻塞性肺疾病患者在内的临床试验揭示了许多关于病情恶化频率的信息,但大多数研究都有局限性,因为它们只根据传统诊断标准招募明确诊断为一种疾病或另一种疾病的患者,这可能会将现实世界中许多具有混合症状的患者排除在外。在这项子分析中,我们比较了日本人群(n = 820)和不包括日本患者的总体人群(n = 10406)的阻塞性肺部疾病患者特征。结果在大多数医生评估的疾病严重程度和所有诊断中,日本人群的病情恶化程度低于总体人群。在慢性阻塞性肺病和哮喘+慢性阻塞性肺病患者中,病情加重频率的差异更为明显。在所有诊断中,与总体人群相比,日本人群年龄更大、以前吸烟率更高、体重指数(BMI)更低、呼吸道症状更少、健康相关生活质量更好。重要的是,我们发现日本哮喘和/或慢性阻塞性肺病患者的病情恶化程度明显低于整体患者。我们的研究结果可能有助于制定适合日本的精准医疗和指南。
{"title":"Exacerbation rates in Japanese patients with obstructive lung disease: A subanalysis of the prospective, observational NOVELTY study","authors":"Tomotaka Kawayama ,&nbsp;Kenichi Takahashi ,&nbsp;Toshikazu Ikeda ,&nbsp;Kenya Fukui ,&nbsp;Naoyuki Makita ,&nbsp;Naoki Tashiro ,&nbsp;Junpei Saito ,&nbsp;Toshihiro Shirai ,&nbsp;Hiromasa Inoue","doi":"10.1016/j.alit.2023.08.003","DOIUrl":"10.1016/j.alit.2023.08.003","url":null,"abstract":"<div><h3>Background</h3><p>Although clinical trials including asthma and COPD patients have revealed much about exacerbation frequencies, most studies are limited in that they recruited patients only with a clear diagnosis of one disease or the other, based on conventional diagnostic criteria, which may exclude many real-world patients with mixed symptoms.</p></div><div><h3>Methods</h3><p>NOVELTY is a global prospective observational study of patients with asthma and/or COPD from real-world practice. In this subanalysis, we compared patient characteristics of obstructive pulmonary diseases between the Japanese population (n = 820) and the overall population excluding Japanese patients (n = 10,406).</p></div><div><h3>Results</h3><p>The Japanese population had fewer exacerbations than the overall population across most of the physician-assessed disease severities and all diagnoses. The difference in exacerbation frequencies was more prominent in patients with COPD and asthma + COPD. The Japanese population was older, had higher former smoking rates, lower BMI, fewer respiratory symptoms, and better health-related quality of life compared with the overall population across all diagnoses.</p></div><div><h3>Conclusions</h3><p>We clarified differences in patient characteristics among patients with asthma and/or COPD in Japan compared with non-Japanese patients. Importantly, we found that Japanese patients with asthma and/or COPD had significantly fewer exacerbations compared with patients overall. The results from our study may contribute to the development of precision medicine and guidelines specific to Japan.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023000795/pdfft?md5=be10da29b2ced0ae540b40dff2426a29&pid=1-s2.0-S1323893023000795-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10500248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation 呼吸系统中的 CYP27A1-27- 羟基胆固醇轴是屋尘螨诱发过敏性气道炎症的原因之一
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.08.005
Tatsunori Ito , Tomohiro Ichikawa , Mitsuhiro Yamada, Yuichiro Hashimoto, Naoya Fujino, Tadahisa Numakura, Yusaku Sasaki, Ayumi Suzuki, Katsuya Takita, Hirohito Sano, Yorihiko Kyogoku, Takuya Saito, Akira Koarai, Tsutomu Tamada, Hisatoshi Sugiura

Background

27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma.

Methods

House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA.

Results

The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin.

Conclusions

The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.

背景27-羟基胆固醇(27-HC)来源于甾醇 27- 羟化酶(CYP27A1),具有促炎生物活性,与慢性阻塞性肺病的氧化应激和慢性炎症有关。然而,CYP27A1- 27-HC 轴在哮喘中的调节作用尚不清楚。本研究旨在阐明该轴对哮喘病理生理学的贡献。方法给 C57BL/6 小鼠鼻内注射屋尘螨(HDM)提取物,并通过免疫染色法分析气道中 CYP27A1 的表达。在小鼠模型中分析了预处理 PBS 或 CYP27A1 抑制剂对支气管肺泡灌洗液(BALF)中细胞组分的影响。在体外,用 HDM 处理 BEAS-2B 细胞并检测 CYP27A1 的表达水平。此外,还分析了 27-HC 对细胞中 E-cadherin 和 ZO-1 表达的影响。结果服用 HDM 增加了小鼠气道中 CYP27A1 的表达以及嗜酸性粒细胞在 BALF 中的数量。CYP27A1 抑制剂可改善 HDM 引起的 BALF 中嗜酸性粒细胞数量的增加。用 HDM 处理会增加 BEAS-2B 细胞中 CYP27A1 的表达。结论 本研究结果表明,航空过敏原可增强 CYP27A1 的诱导,通过产生 27-HC 导致过敏性气道炎症和气道上皮紧密连接的破坏。
{"title":"CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation","authors":"Tatsunori Ito ,&nbsp;Tomohiro Ichikawa ,&nbsp;Mitsuhiro Yamada,&nbsp;Yuichiro Hashimoto,&nbsp;Naoya Fujino,&nbsp;Tadahisa Numakura,&nbsp;Yusaku Sasaki,&nbsp;Ayumi Suzuki,&nbsp;Katsuya Takita,&nbsp;Hirohito Sano,&nbsp;Yorihiko Kyogoku,&nbsp;Takuya Saito,&nbsp;Akira Koarai,&nbsp;Tsutomu Tamada,&nbsp;Hisatoshi Sugiura","doi":"10.1016/j.alit.2023.08.005","DOIUrl":"10.1016/j.alit.2023.08.005","url":null,"abstract":"<div><h3>Background</h3><p>27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma.</p></div><div><h3>Methods</h3><p>House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA.</p></div><div><h3>Results</h3><p>The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin.</p></div><div><h3>Conclusions</h3><p>The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023000813/pdfft?md5=ee80527c3459bce46463add890d50d27&pid=1-s2.0-S1323893023000813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Asian birth cohort studies 亚洲出生队列研究
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.11.008
Yukihiro Ohya (Guest Editor, Allergology International)
{"title":"Asian birth cohort studies","authors":"Yukihiro Ohya (Guest Editor, Allergology International)","doi":"10.1016/j.alit.2023.11.008","DOIUrl":"10.1016/j.alit.2023.11.008","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S132389302300120X/pdfft?md5=b6d6d354672dae7dbf1191b609a8bb24&pid=1-s2.0-S132389302300120X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiota and fecal metabolites in sustained unresponsiveness by oral immunotherapy in school-age children with cow's milk allergy 对牛奶过敏的学龄儿童口服免疫疗法持续无效时的肠道微生物群和粪便代谢物
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.10.001
Ryohei Shibata , Naoka Itoh , Yumiko Nakanishi , Tamotsu Kato , Wataru Suda , Mizuho Nagao , J-OIT group , Tsutomu Iwata , Hideo Yoshida , Masahira Hattori , Takao Fujisawa , Naoki Shimojo , Hiroshi Ohno

Background

Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA.

Methods

We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules.

Results

During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT.

Conclusions

In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

背景口服免疫疗法(OIT)可以改善牛奶过敏(CMA),但要达到持续无应答(SU)却很困难。关于 CMA 的发病机制,最近的研究表明肠道微生物群(Mb)和粪便中的水溶性代谢物(WSMs)非常重要,这促使我们确定临床和肠道环境因素的变化对 OIT 治疗 CMA 后获得 SU 的重要性。我们将 SU 定义为在 OIT 后进行的双盲安慰剂对照食物挑战中能够食用超过目标剂量的牛奶,然后再进行为期两周的回避。我们纵向收集了 175 份粪便标本,并将微生物组和代谢组数据聚类为 29 个 Mb 模块和 12 个 WSM 模块。然而,在 32 名参与者中,有 4 人因不良反应而退出,只有 7 人被评为 SU。肠道环境因素在 OIT 期间发生了变化,但只是在开始时,并在结束时恢复到基线水平。在这些因素中,牛奶和酪蛋白特异性 IgE 以及双歧杆菌优势模块与 SU 相关(牛奶和酪蛋白特异性 IgE;10 kUA/L 增量的 OR 为 0.67 和 0.66;95%CI 为 0.41-0.93 和 0.42-0.90 ;双歧杆菌优势模块;0.结论在这项研究中,我们确定了与 CM-OIT 中 SU 获得相关的临床和肠道环境因素。
{"title":"Gut microbiota and fecal metabolites in sustained unresponsiveness by oral immunotherapy in school-age children with cow's milk allergy","authors":"Ryohei Shibata ,&nbsp;Naoka Itoh ,&nbsp;Yumiko Nakanishi ,&nbsp;Tamotsu Kato ,&nbsp;Wataru Suda ,&nbsp;Mizuho Nagao ,&nbsp;J-OIT group ,&nbsp;Tsutomu Iwata ,&nbsp;Hideo Yoshida ,&nbsp;Masahira Hattori ,&nbsp;Takao Fujisawa ,&nbsp;Naoki Shimojo ,&nbsp;Hiroshi Ohno","doi":"10.1016/j.alit.2023.10.001","DOIUrl":"10.1016/j.alit.2023.10.001","url":null,"abstract":"<div><h3>Background</h3><p>Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA.</p></div><div><h3>Methods</h3><p>We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules.</p></div><div><h3>Results</h3><p>During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the <em>Bifidobacterium</em>-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kU<sub>A</sub>/L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; <em>Bifidobacterium</em>-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT.</p></div><div><h3>Conclusions</h3><p>In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023001053/pdfft?md5=356eee74a5c3380b1d6cecd2fb3bc1ae&pid=1-s2.0-S1323893023001053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135221120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma 单核细胞和巨噬细胞胞外捕获器对重症哮喘中性粒细胞气道炎症的贡献
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.alit.2023.06.004
Quang Luu Quoc , Thi Bich Tra Cao , Ji-Young Moon , Jae-Hyuk Jang , Yoo Seob Shin , Youngwoo Choi , Min Sook Ryu , Hae-Sim Park

Background

Increased blood/sputum neutrophil counts are related to poor clinical outcomes of severe asthma (SA), where we hypothesized that classical monocytes (CMs)/CM-derived macrophages (Mφ) are involved. We aimed to elucidate the mechanisms of how CMs/Mφ induce the activation of neutrophils/innate lymphoid cells (ILCs) in SA.

Methods

Serum levels of monocyte chemoattractant protein-1 (MCP-1) and soluble suppression of tumorigenicity 2 (sST2) were measured from 39 patients with SA and 98 those with nonsevere asthma (NSA). CMs/Mφ were isolated from patients with SA (n = 19) and those with NSA (n = 18) and treated with LPS/interferon-gamma. Monocyte/M1Mφ extracellular traps (MoETs/M1ETs) were evaluated by western blotting, immunofluorescence, and PicoGreen assay. The effects of MoETs/M1ETs on neutrophils, airway epithelial cells (AECs), ILC1, and ILC3 were assessed in vitro and in vivo.

Results

The SA group had significantly higher CM counts with increased migration as well as higher levels of serum MCP-1/sST2 than the NSA group. Moreover, the SA group had significantly greater production of MoETs/M1ETs (from CMs/M1Mφ) than the NSA group. The levels of MoETs/M1ETs were positively correlated with blood neutrophils and serum levels of MCP-1/sST2, but negatively correlated with FEV1%. In vitro/in vivo studies demonstrated that MoETs/M1ETs could activate AECs, neutrophils, ILC1, and ILC3 by increased migration as well as proinflammatory cytokine production.

Conclusions

CM/Mφ-derived MoETs/M1ETs could contribute to asthma severity by enhancing neutrophilic airway inflammation in SA, where modulating CMs/Mφ may be a potential therapeutic option.

背景血液/痰中性粒细胞计数增加与重症哮喘(SA)的不良临床预后有关,我们推测这与经典单核细胞(CMs)/CM衍生巨噬细胞(Mφ)有关。我们的目的是阐明 CMs/Mφ 在 SA 中如何诱导中性粒细胞/innate 淋巴细胞(ILCs)活化的机制。方法测量了 39 名 SA 患者和 98 名非严重哮喘(NSA)患者血清中单核细胞趋化蛋白-1(MCP-1)和可溶性抑制肿瘤生成 2(sST2)的水平。从 SA(19 人)和 NSA(18 人)患者体内分离出 CMs/Mφ,并用 LPS/γ 干扰素处理。单核细胞/M1Mφ胞外捕集器(MoETs/M1ETs)通过免疫印迹、免疫荧光和 PicoGreen 检测进行评估。结果与 NSA 组相比,SA 组的中性粒细胞数量显著增加,迁移率和血清 MCP-1/sST2 水平也有所提高。此外,SA 组的 MoETs/M1ETs 产量(来自 CMs/M1Mφ)明显高于 NSA 组。MoETs/M1ETs 的水平与血液中性粒细胞和血清中 MCP-1/sST2 的水平呈正相关,但与 FEV1% 呈负相关。体外/体内研究表明,MoETs/M1ETs 可通过增加迁移和促炎细胞因子的产生来激活 AECs、中性粒细胞、ILC1 和 ILC3。
{"title":"Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma","authors":"Quang Luu Quoc ,&nbsp;Thi Bich Tra Cao ,&nbsp;Ji-Young Moon ,&nbsp;Jae-Hyuk Jang ,&nbsp;Yoo Seob Shin ,&nbsp;Youngwoo Choi ,&nbsp;Min Sook Ryu ,&nbsp;Hae-Sim Park","doi":"10.1016/j.alit.2023.06.004","DOIUrl":"10.1016/j.alit.2023.06.004","url":null,"abstract":"<div><h3>Background</h3><p>Increased blood/sputum neutrophil counts are related to poor clinical outcomes of severe asthma (SA), where we hypothesized that classical monocytes (CMs)/CM-derived macrophages (Mφ) are involved. We aimed to elucidate the mechanisms of how CMs/Mφ induce the activation of neutrophils/innate lymphoid cells (ILCs) in SA.</p></div><div><h3>Methods</h3><p>Serum levels of monocyte chemoattractant protein-1 (MCP-1) and soluble suppression of tumorigenicity 2 (sST2) were measured from 39 patients with SA and 98 those with nonsevere asthma (NSA). CMs/Mφ were isolated from patients with SA (n = 19) and those with NSA (n = 18) and treated with LPS/interferon-gamma. Monocyte/M1Mφ extracellular traps (MoETs/M1ETs) were evaluated by western blotting, immunofluorescence, and PicoGreen assay. The effects of MoETs/M1ETs on neutrophils, airway epithelial cells (AECs), ILC1, and ILC3 were assessed <em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Results</h3><p>The SA group had significantly higher CM counts with increased migration as well as higher levels of serum MCP-1/sST2 than the NSA group. Moreover, the SA group had significantly greater production of MoETs/M1ETs (from CMs/M1Mφ) than the NSA group. The levels of MoETs/M1ETs were positively correlated with blood neutrophils and serum levels of MCP-1/sST2, but negatively correlated with FEV<sub>1</sub>%. <em>In vitro</em>/<em>in vivo</em> studies demonstrated that MoETs/M1ETs could activate AECs, neutrophils, ILC1, and ILC3 by increased migration as well as proinflammatory cytokine production.</p></div><div><h3>Conclusions</h3><p>CM/Mφ-derived MoETs/M1ETs could contribute to asthma severity by enhancing neutrophilic airway inflammation in SA, where modulating CMs/Mφ may be a potential therapeutic option.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023000680/pdfft?md5=5c5a9461356e2db012f589b18c7e4f88&pid=1-s2.0-S1323893023000680-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring patient background and biomarkers associated with the development of dupilumab-associated conjunctivitis and blepharitis 探索与杜匹单抗相关结膜炎和睑缘炎发病相关的患者背景和生物标志物。
IF 6.8 2区 医学 Q1 Medicine Pub Date : 2023-12-27 DOI: 10.1016/j.alit.2023.12.001
Makiko Kido-Nakahara , Daisuke Onozuka , Kenji Izuhara , Hidehisa Saeki , Satoshi Nunomura , Motoi Takenaka , Mai Matsumoto , Yoko Kataoka , Rai Fujimoto , Sakae Kaneko , Eishin Morita , Akio Tanaka , Ryo Saito , Tatsuro Okano , Tomomitsu Miyagaki , Natsuko Aoki , Kimiko Nakajima , Susumu Ichiyama , Kyoko Tonomura , Yukinobu Nakagawa , Takeshi Nakahara
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引用次数: 0
期刊
Allergology International
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