Chan Edward D, Iseman Michael D
Department of Medicine, National Jewish Health, Denver, Colorado 80206, USA.
Gend Med. 2010 Feb;7(1):5-18. doi: 10.1016/j.genm.2010.01.005.
Nontuberculous mycobacteria (NTM) are environmental microbes that are associated with a variety of human diseases, particularly chronic lung infections. Over the past several decades, NTM lung disease has been increasingly seen in postmenopausal women with slender body habitus.
This article reviewed the clinical and experimental evidence that supports the observation that thin older women (aged 50-80 years) are predisposed to NTM lung disease. We posited 3 potential pathways for this predisposition: relative estrogen deficiency, abnormal levels of adipokines that alter immune responses, and abnormal expression of transforming growth factor-beta (TGF-beta) related to fibrillin anomalies similar to Marfan syndrome (MFS).
Using the PubMed database, a literature search was performed (all publications up to July 2009) by pairing the key phrase nontuberculous mycobacteria with weight, malnutrition, female gender, body habitus, leptin, adipokines, estrogen, menopause, postmenopausal, or body mass index. Non-English-language articles were included if their abstracts were in English. Relevant articles were also identified from the abstracts.
Published case reports and series indicate that in the past 20 years, NTM lung disease has been recognized in disproportionately increased numbers in postmenopausal women. Among these patients, slender body habitus and thoracic cage abnormalities, such as pectus excavatum and scoliosis, are commonly described. Notably, no long-term prospective clinical studies exist to corroborate that low weight is an independent risk factor for NTM lung disease. However, based on the findings of a limited number of experimental studies, we hypothesize that decreased leptin, increased adiponectin, and/or decreased estrogen in older women with slender body habitus may account for their increased susceptibility to NTM infections. We further speculate that in some patients with features mindful of MPS (slender, scoliosis, pectus excavatum, or mitral valve prolapse), there may be anomalies of fibrillin, similar to MFS, that lead to the expression of the immunosuppressive cytokine TGP-beta further increasing their susceptibility to NTM.
It is likely that both sufficient environmental exposure and host susceptibility are required for the establishment of NTM lung disease. The observation that NTM lung infections are more common in slender, older women without any overt immune defects suggests that abnormal expression of adipokines, sex hormones, and/or TGF-beta may play an important role in their susceptibility.
非结核分枝杆菌（NTM）是环境微生物，与多种人类疾病相关，尤其是慢性肺部感染。在过去几十年中，NTM肺病在绝经后体型消瘦的女性中越来越常见。
本文综述了支持以下观察结果的临床和实验证据：瘦的老年女性（50 - 80岁）易患NTM肺病。我们提出了这种易感性的3条潜在途径：相对雌激素缺乏、改变免疫反应的脂肪因子水平异常，以及与类似于马凡综合征（MFS）的原纤维蛋白异常相关的转化生长因子-β（TGF-β）异常表达。
使用PubMed数据库，通过将关键词非结核分枝杆菌与体重、营养不良、女性性别、体型、瘦素、脂肪因子、雌激素、绝经、绝经后或体重指数配对进行文献检索（截至2009年7月的所有出版物）。如果非英语文章的摘要为英文，则纳入。相关文章也从摘要中识别。
已发表的病例报告和系列研究表明，在过去20年中，绝经后女性中NTM肺病的确诊人数不成比例地增加。在这些患者中，常见体型消瘦和胸廓异常，如漏斗胸和脊柱侧弯。值得注意的是，尚无长期前瞻性临床研究证实低体重是NTM肺病的独立危险因素。然而，基于有限数量的实验研究结果，我们推测体型消瘦的老年女性中瘦素降低、脂联素增加和/或雌激素降低可能是其对NTM感染易感性增加的原因。我们进一步推测，在一些具有马凡综合征特征（消瘦、脊柱侧弯、漏斗胸或二尖瓣脱垂）的患者中，可能存在类似于MFS的原纤维蛋白异常，导致免疫抑制细胞因子TGP-β表达，进一步增加其对NTM的易感性。
NTM肺病的发生可能既需要充分的环境暴露，也需要宿主易感性。NTM肺部感染在体型消瘦、无明显免疫缺陷的老年女性中更常见这一观察结果表明，脂肪因子、性激素和/或TGF-β的异常表达可能在其易感性中起重要作用。
