A. Yii, T. Tay, S. Puah, H. Lim, A. Li, P. Lau, Rae-Ann Tan, L. Neo, K. Chung, M. Koh
An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation.
{"title":"Blood eosinophil count correlates with severity of respiratory failure in life‐threatening asthma and predicts risk of subsequent exacerbations","authors":"A. Yii, T. Tay, S. Puah, H. Lim, A. Li, P. Lau, Rae-Ann Tan, L. Neo, K. Chung, M. Koh","doi":"10.1111/cea.13465","DOIUrl":"https://doi.org/10.1111/cea.13465","url":null,"abstract":"An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"101 1","pages":"1578 - 1586"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77341338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Ishii, M. Muroi, K. Horiguchi, K. Tanamoto, T. Nagase, N. Yamashita
Type 2 innate lymphoid cells (ILC2s) are one of the sources of IL‐5 and IL‐13 in allergic airway inflammation. Innate immune receptors such as Toll‐like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL‐33 production, but a direct effect of TLRs on ILC2s remains to be elucidated.
{"title":"Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics","authors":"T. Ishii, M. Muroi, K. Horiguchi, K. Tanamoto, T. Nagase, N. Yamashita","doi":"10.1111/cea.13490","DOIUrl":"https://doi.org/10.1111/cea.13490","url":null,"abstract":"Type 2 innate lymphoid cells (ILC2s) are one of the sources of IL‐5 and IL‐13 in allergic airway inflammation. Innate immune receptors such as Toll‐like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL‐33 production, but a direct effect of TLRs on ILC2s remains to be elucidated.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"9 1","pages":"1624 - 1632"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74427238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The symptoms of chronic urticaria, be it chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CindU), are mediated primarily by the actions of histamine on H1 receptors located on endothelial cells (the weal) and on sensory nerves (neurogenic flare and pruritus). Thus, second‐generation H1 antihistamines (sgAHs) are the primary treatment of these conditions. However, many patients are poorly responsive to licensed doses of antihistamines. In these patients, the current EAACI/GA2LEN/EDF/WAO guideline for urticaria suggests updosing of sgAHs up to fourfold. However, such updosing is off‐label and the responsibility resides with the prescribing physician. Therefore, the safety of the drug when used above its licensed dose is of paramount importance. An important aspect of safety is potential cardiotoxicity. This problem was initially identified some 20 years ago with cardiotoxic deaths occurring with astemizole and terfenadine, two early sgAHs. In this review, we discuss the mechanisms and assessments of potential cardiotoxicity of H1 antihistamines when updosed to four times their licensed dose. In particular, we have focused on the potential of H1 antihistamines to block hERG (human Ether‐a‐go‐go‐Related Gene) voltage‐gated K+ channels, also known as Kv11.1 channels according to the IUPHAR classification. Blockade of these channels causes QT prolongation leading to torsade de pointes that may possibly degenerate into ventricular fibrillation and sudden death. We considered in detail bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, loratadine, desloratadine, mizolastine and rupatadine and concluded that all these drugs have an excellent safety profile with no evidence of cardiotoxicity even when updosed up to four times their standard licensed dose, provided that the prescribers carefully consider and rule out potential risk factors for cardiotoxicity, such as the presence of inherited long QT syndrome, older age, cardiovascular disorders, hypokalemia and hypomagnesemia, or the use of drugs that either have direct QT prolonging effects or inhibit sgAH metabolism.
慢性荨麻疹的症状，无论是慢性自发性荨麻疹(CSU)还是慢性诱导性荨麻疹(CindU)，主要是由组胺作用于内皮细胞(皮肤)和感觉神经(神经源性耀斑和瘙痒)上的H1受体介导的。因此，第二代H1抗组胺药(sgAHs)是这些疾病的主要治疗方法。然而，许多患者对许可剂量的抗组胺药反应不良。在这些患者中，目前的EAACI/GA2LEN/EDF/WAO荨麻疹指南建议将sgAHs剂量增加4倍。然而，这样的增加是标签外的，责任在于开处方的医生。因此，超过许可剂量使用药物的安全性至关重要。安全性的一个重要方面是潜在的心脏毒性。这一问题最初是在大约20年前发现的，当时发生在阿司咪唑和特非那定这两种早期sgAHs的心脏毒性死亡。在这篇综述中，我们讨论了H1抗组胺药增加到许可剂量的四倍时的潜在心脏毒性的机制和评估。特别地，我们关注了H1抗组胺药阻断hERG(人Ether - a - go - go - Related Gene)电压门控K+通道的潜力，根据IUPHAR分类，也称为Kv11.1通道。这些通道的阻断导致QT延长，导致点扭转，可能退化为心室颤动和猝死。我们详细考虑了bilastine，西替利嗪，左西替利嗪，ebastine，非索非那定，氯雷他定，地氯雷他定，米索拉斯汀和鲁帕他定，并得出结论，所有这些药物都具有极好的安全性，即使增加到其标准许可剂量的四倍，也没有心脏毒性的证据，只要处方者仔细考虑并排除心脏毒性的潜在危险因素，如遗传性长QT间期综合征，年龄较大，心血管疾病、低钾血症和低镁血症，或使用具有直接QT间期延长作用或抑制sgAH代谢的药物。
{"title":"Cardiac safety of second‐generation H1‐antihistamines when updosed in chronic spontaneous urticaria","authors":"M. Cataldi, M. Maurer, M. Taglialatela, M. Church","doi":"10.1111/cea.13500","DOIUrl":"https://doi.org/10.1111/cea.13500","url":null,"abstract":"The symptoms of chronic urticaria, be it chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CindU), are mediated primarily by the actions of histamine on H1 receptors located on endothelial cells (the weal) and on sensory nerves (neurogenic flare and pruritus). Thus, second‐generation H1 antihistamines (sgAHs) are the primary treatment of these conditions. However, many patients are poorly responsive to licensed doses of antihistamines. In these patients, the current EAACI/GA2LEN/EDF/WAO guideline for urticaria suggests updosing of sgAHs up to fourfold. However, such updosing is off‐label and the responsibility resides with the prescribing physician. Therefore, the safety of the drug when used above its licensed dose is of paramount importance. An important aspect of safety is potential cardiotoxicity. This problem was initially identified some 20 years ago with cardiotoxic deaths occurring with astemizole and terfenadine, two early sgAHs. In this review, we discuss the mechanisms and assessments of potential cardiotoxicity of H1 antihistamines when updosed to four times their licensed dose. In particular, we have focused on the potential of H1 antihistamines to block hERG (human Ether‐a‐go‐go‐Related Gene) voltage‐gated K+ channels, also known as Kv11.1 channels according to the IUPHAR classification. Blockade of these channels causes QT prolongation leading to torsade de pointes that may possibly degenerate into ventricular fibrillation and sudden death. We considered in detail bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, loratadine, desloratadine, mizolastine and rupatadine and concluded that all these drugs have an excellent safety profile with no evidence of cardiotoxicity even when updosed up to four times their standard licensed dose, provided that the prescribers carefully consider and rule out potential risk factors for cardiotoxicity, such as the presence of inherited long QT syndrome, older age, cardiovascular disorders, hypokalemia and hypomagnesemia, or the use of drugs that either have direct QT prolonging effects or inhibit sgAH metabolism.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"10 1","pages":"1615 - 1623"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91080884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Lauzon-Joset, K. T. Mincham, A. Abad, B. Short, P. Holt, D. Strickland, J. Leffler
The prevalence and severity of asthma, particularly the most common (atopic) form of the disease, increase amongst females but not males after puberty, and asthma activity also changes throughout the menstrual cycle and during pregnancy. The contribution of female sex hormones to asthma pathogenesis is incompletely understood.
{"title":"Oestrogen amplifies pre‐existing atopy‐associated Th2 bias in an experimental asthma model","authors":"J. Lauzon-Joset, K. T. Mincham, A. Abad, B. Short, P. Holt, D. Strickland, J. Leffler","doi":"10.1111/cea.13544","DOIUrl":"https://doi.org/10.1111/cea.13544","url":null,"abstract":"The prevalence and severity of asthma, particularly the most common (atopic) form of the disease, increase amongst females but not males after puberty, and asthma activity also changes throughout the menstrual cycle and during pregnancy. The contribution of female sex hormones to asthma pathogenesis is incompletely understood.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"8 1","pages":"391 - 400"},"PeriodicalIF":0.0,"publicationDate":"2019-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81737358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection.
甘露醇吸入试验是针对嗜酸性气道炎症的哮喘患者的，这一因素与深度吸入支气管保护的发展呈负相关。
{"title":"The effect of deep inhalation on mannitol responsiveness","authors":"Christianne M Blais, B. Davis, D. Cockcroft","doi":"10.1111/cea.13543","DOIUrl":"https://doi.org/10.1111/cea.13543","url":null,"abstract":"Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"10 1","pages":"308 - 314"},"PeriodicalIF":0.0,"publicationDate":"2019-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74148391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Almqvist, S. Ekberg, S. Rhedin, F. Fang, T. Fall, C. Lundholm
Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.
{"title":"Season of birth, childhood asthma and allergy in a nationwide cohort—Mediation through lower respiratory infections","authors":"C. Almqvist, S. Ekberg, S. Rhedin, F. Fang, T. Fall, C. Lundholm","doi":"10.1111/cea.13542","DOIUrl":"https://doi.org/10.1111/cea.13542","url":null,"abstract":"Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"3 1","pages":"222 - 230"},"PeriodicalIF":0.0,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81703885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the overwhelming evidence showing the influence of sex or obesity in the development of respiratory diseases in humans and animals, the mechanisms by which these combined two factors influence allergic asthma are not well understood.
{"title":"Sex differences in the influence of obesity on a murine model of allergic lung inflammation","authors":"R. e-Lacerda, G. Anhê, C. Page, Y. Riffo-Vasquez","doi":"10.1111/cea.13541","DOIUrl":"https://doi.org/10.1111/cea.13541","url":null,"abstract":"Despite the overwhelming evidence showing the influence of sex or obesity in the development of respiratory diseases in humans and animals, the mechanisms by which these combined two factors influence allergic asthma are not well understood.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"93 1","pages":"256 - 266"},"PeriodicalIF":0.0,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80516860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Tacquard, W. Oulehri, O. Collange, L. H. Garvey, S. Nicoll, N. Tuzin, B. Gény, P. Mertes
In some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet‐activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity.
{"title":"Treatment with a platelet‐activating factor receptor antagonist improves hemodynamics and reduces epinephrine requirements, in a lethal rodent model of anaphylactic shock","authors":"C. Tacquard, W. Oulehri, O. Collange, L. H. Garvey, S. Nicoll, N. Tuzin, B. Gény, P. Mertes","doi":"10.1111/cea.13540","DOIUrl":"https://doi.org/10.1111/cea.13540","url":null,"abstract":"In some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet‐activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"33 1","pages":"383 - 390"},"PeriodicalIF":0.0,"publicationDate":"2019-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77276009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Esnault, J. Leet, M. Johansson, Karina T. Barretto, P. Fichtinger, F. J. Fogerty, K. Bernau, S. Mathur, D. Mosher, N. Sandbo, N. Jarjour
The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell‐free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that eosinophils have lysed and released cellular content, likely harming tissues.
{"title":"Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho‐associated protein kinase signalling","authors":"S. Esnault, J. Leet, M. Johansson, Karina T. Barretto, P. Fichtinger, F. J. Fogerty, K. Bernau, S. Mathur, D. Mosher, N. Sandbo, N. Jarjour","doi":"10.1111/cea.13538","DOIUrl":"https://doi.org/10.1111/cea.13538","url":null,"abstract":"The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell‐free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that eosinophils have lysed and released cellular content, likely harming tissues.","PeriodicalId":10148,"journal":{"name":"Clinical & Experimental Allergy","volume":"13 1","pages":"198 - 212"},"PeriodicalIF":0.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81732091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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