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烟曲霉致敏在难治性哮喘患者中的临床意义

The Clinical Implications of Aspergillus Fumigatus Sensitization in Difficult-To-Treat Asthma Patients.

作者信息

Mistry Heena, Ajsivinac Soberanis Hilda Maria, Kyyaly Mohammad Aref, Azim Adnan, Barber Clair, Knight Deborah, Newell Colin, Haitchi Hans Michael, Wilkinson Tom, Howarth Peter, Seumois Grégory, Vijayanand Pandurangan, Arshad S Hasan, Kurukulaaratchy Ramesh J

机构信息

Clinical and Experimental Sciences Department, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre at University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Asthma, Allergy and Clinical Immunology Department, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; La Jolla Institute of Immunology, La Jolla, Calif; The David Hide Asthma & Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.

Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

出版信息

J Allergy Clin Immunol Pract. 2021 Dec;9(12):4254-4267.e10. doi: 10.1016/j.jaip.2021.08.038. Epub 2021 Sep 14.

Abstract

BACKGROUND

Fungal sensitivity has been associated with severe asthma outcomes. However, the clinical implication of Aspergillus fumigatus sensitization in difficult-to-treat (or difficult) asthma is unclear.

OBJECTIVES

To characterize the clinical implications of A fumigatus sensitization in a large difficult asthma cohort.

METHODS

Participants who underwent both skin prick and specific IgE testing to A fumigatus (n = 318) from the longitudinal real-life Wessex AsThma CoHort of difficult asthma, United Kingdom, were characterized by A fumigatus sensitization (either positive skin prick test result or specific IgE) and allergic bronchopulmonary aspergillosis status using clinical/pathophysiological disease measures.

RESULTS

A fumigatus sensitization was found in 23.9% (76 of 318) of patients with difficult asthma. Compared with A fumigatus nonsensitized subjects, those with sensitization were significantly more often male (50% vs 31%), older (58 years) with longer asthma duration (33 years), higher maintenance oral corticosteroid (39.7%) and asthma biologic use (27.6%), raised current/maximum log total IgE+1 (2.43/2.72 IU/L), worse prebronchodilator airflow obstruction (FEV 62.2% predicted, FEV/forced vital capacity 61.2%, forced expiratory flow between 25% and 75% exhalation 30.9% predicted), and frequent radiological bronchiectasis (40%), but had less psychophysiologic comorbidities. Allergic bronchopulmonary aspergillosis diagnosis was associated with higher treatment needs and stronger eosinophilic signals. Factors independently associated with A fumigatus sensitization in difficult asthma included maintenance oral corticosteroid use (odds ratio [OR], 3.34) and maximum log total IgE+1 (OR, 4.30), whereas for allergic bronchopulmonary aspergillosis included maintenance oral corticosteroid use (OR, 6.98), maximum log total IgE+1 (OR, 4.65), and radiological bronchiectasis (OR, 4.08).

CONCLUSIONS

A fumigatus sensitization in difficult asthma identifies a more severe form of airways disease associated with greater morbidity, treatment need, and airways dysfunction/damage, but fewer psychophysiologic comorbidities. Screening of A fumigatus status should be an early element in the comprehensive assessment of patients with difficult asthma.

摘要

背景

真菌敏感性与严重哮喘结局相关。然而,烟曲霉致敏在难治性(或重度)哮喘中的临床意义尚不清楚。

目的

描述在一大群难治性哮喘患者中烟曲霉致敏的临床意义。

方法

对来自英国韦塞克斯难治性哮喘纵向真实世界队列中接受了针对烟曲霉的皮肤点刺试验和特异性IgE检测的参与者(n = 318),根据烟曲霉致敏情况(皮肤点刺试验结果阳性或特异性IgE阳性)以及变应性支气管肺曲霉病状态,采用临床/病理生理疾病指标进行特征分析。

结果

在318例难治性哮喘患者中,23.9%(76例)存在烟曲霉致敏。与未致敏的受试者相比,致敏者男性比例显著更高(50%对31%),年龄更大(58岁),哮喘病程更长(33年),口服糖皮质激素维持治疗使用率更高(39.7%),哮喘生物制剂使用率更高(27.6%),当前/最大log总IgE + 1升高(2.43/2.72 IU/L),支气管舒张前气流受限更严重(预测FEV为62.2%,FEV/用力肺活量为61.2%,呼气25%至75%时的用力呼气流量为预测值的30.9%),放射性支气管扩张更常见(40%),但心理生理合并症较少。变应性支气管肺曲霉病诊断与更高的治疗需求和更强的嗜酸性粒细胞信号相关。难治性哮喘中与烟曲霉致敏独立相关的因素包括口服糖皮质激素维持治疗的使用(比值比[OR],3.34)和最大log总IgE + 1(OR,4.30),而对于变应性支气管肺曲霉病,相关因素包括口服糖皮质激素维持治疗的使用(OR,6.98)、最大log总IgE + 1(OR,4.65)和放射性支气管扩张(OR,4.08)。

结论

难治性哮喘中的烟曲霉致敏表明存在一种更严重的气道疾病形式,与更高的发病率、治疗需求以及气道功能障碍/损伤相关,但心理生理合并症较少。对烟曲霉状态的筛查应是难治性哮喘患者综合评估的早期内容。

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