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Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway
Journal of Cystic Fibrosis ( IF 5.4 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.jcf.2020.06.016
Prithwiraj De 1 , Anita G Amin 1 , Barbara Graham 1 , Stacey L Martiniano 2 , Silvia M Caceres 3 , Katie R Poch 3 , Marion C Jones 3 , Milene T Saavedra 3 , Kenneth C Malcolm 3 , Jerry A Nick 3 , Delphi Chatterjee 1
Affiliation  

BACKGROUND Individuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. METHODS Urine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. CONCLUSION These findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.

中文翻译:

尿液脂阿拉伯甘露聚糖作为 CF 气道中 NTM 感染低风险的标志物

背景 囊性纤维化 (CF) 患者是肺部感染非结核分枝杆菌 (NTM) 的最脆弱人群。目前对治疗反应的筛查、诊断和评估依赖于传统的培养技术,但对 CF 中 NTM 的痰液分析具有挑战性,并且与低灵敏度相关。细胞壁脂阿拉伯甘露聚糖 (LAM) 是一种存在于所有分枝杆菌物种中的脂多糖,已被验证为尿液中活动性结核分枝杆菌感染的生物标志物。方法 通过气道培养物对来自 CF 队列(n = 44)的尿液进行 NTM 感染状态的充分表征,通过气相色谱/质谱法分析 LAM。所有 NTM 痰培养阳性的受试者的尿液中都含有不同量的 LAM。在从未有过阳性培养的受试者中未检测到 LAM (14/45)。一名最初归类为 NTM 痰阴性的个体随后在最初的尿液 LAM 检测后 657 天发展为 NTM 病。重复尿液 LAM 检测变为阳性,这与她的 NTM 状态呈阳性有关。感染 M. abscessus 亚种的受试者的 LAM 量高于感染 M. avium complex (MAC) 的受试者。与疾病活动或治疗状态和 LAM 数量没有相关性。使用抗 LAM 抗体的 TB Capture ELISA 在识别具有阳性 NTM 痰培养的个体方面表现出非常差的敏感性。结论 这些发现支持以下结论:与 NTM 感染相关的尿 LAM 可能是一种有用的筛查试验,可用于确定 NTM 痰培养阳性的低风险患者,
更新日期:2020-09-01
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