Rick Eva-Maria, Woolnough Kerry F, Seear Paul J, Fairs Abbie, Satchwell Jack, Richardson Matthew, Monteiro William R, Craner Michelle, Bourne Michelle, Wardlaw Andrew J, Pashley Catherine H
Department of Respiratory Sciences, Institute for Lung Health, Leicester Biomedical Research Centre - Respiratory, University of Leicester, Leicester, UK.
Institute for Lung Health, Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital, University Hospitals of Leicester, Leicester, UK.
Clin Exp Allergy. 2020 Dec;50(12):1325-1341. doi: 10.1111/cea.13722. Epub 2020 Sep 9.
Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques.
To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes.
We amplified the internal transcribed spacer region 2 of the nuclear ribosomal operon to identify the fungal species present. Ninety-seven subjects were recruited and provided sputum (83 asthmatics; 14 healthy subjects), with 29 also undergoing a bronchoscopy. A subset of airway samples were compared with matched outdoor air and mouthwash samples.
Two hundred and six taxa at the species level were identified in sputum, most at low relative abundance. Aspergillus fumigatus, Candida albicans and Mycosphaerella tassiana had the highest relative abundances and were the most prevalent species across all subjects. The airway mycobiota consisted of a complex community with high diversity between individuals. Notable shifts in the balance of fungi detected in the lung were associated with asthma status, asthma duration and biomarkers of inflammation. Aspergillus tubingensis, a member of the Aspergillus niger species complex, was most prevalent from bronchoscopic protected brush samples and significantly associated with a low sputum neutrophilia. Cryptococcus pseudolongus, from the Cryptococcus humicola species complex, was more abundant from bronchoscopy samples than sputum, and differentially more abundant in asthma than health.
The airway mycobiota was dominated by a relatively small number of species, but was distinct from the oropharyngeal mycobiota and air samples. Members of the A. niger and C. humicola species complexes may play unexpected roles in the pathogenesis of asthma.
真菌与哮喘的发生有关，且与严重病情相关。哮喘中真菌种类的全貌尚未得到充分描述，主要源于不敏感的培养技术。
运用高通量测序技术描述有或无真菌致敏的哮喘患者及健康对照者的气道真菌群；比较不同气道部位的样本；确定真菌群是否受室外空气真菌组成的影响；并将研究结果与临床相关结局进行比较。
我们扩增核糖体操纵子的内部转录间隔区2以鉴定存在的真菌种类。招募了97名受试者并采集痰液（83名哮喘患者；14名健康受试者），其中29人还接受了支气管镜检查。将一部分气道样本与配对的室外空气和漱口水样本进行比较。
在痰液中鉴定出206个物种水平的分类单元，大多数相对丰度较低。烟曲霉、白色念珠菌和塔斯马尼亚球腔菌相对丰度最高，是所有受试者中最常见的物种。气道真菌群由个体间具有高度多样性的复杂群落组成。在肺部检测到的真菌平衡的显著变化与哮喘状态、哮喘病程和炎症生物标志物有关。黑曲霉复合种的成员管囊曲霉在支气管镜保护性毛刷样本中最常见，且与低痰中性粒细胞增多显著相关。来自腐殖隐球菌复合种的假长隐球菌在支气管镜样本中比痰液中更丰富，且在哮喘患者中比健康人差异更丰富。
气道真菌群由相对少数的物种主导，但与口咽真菌群和空气样本不同。黑曲霉和腐殖隐球菌复合种的成员可能在哮喘发病机制中发挥意想不到的作用。
