title: Slender, older women appear to be more susceptible to nontuberculous mycobacterial lung disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado 80206, USA. chane@njhealth.org
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Iseman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004198:Disease Susceptibility / Q000276:immunology / Q000382:microbiology; D004967:Estrogens / Q000276:immunology; D005260:Female; D000071837:Fibrillins; D006801:Humans; D020738:Leptin / Q000276:immunology; D008171:Lung Diseases / Q000382:microbiology*; D008840:Microfilament Proteins / Q000502:physiology; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D017698:Postmenopause; D013851:Thinness
chemical_list: D004967:Estrogens; D000071837:Fibrillins; D020738:Leptin; D008840:Microfilament Proteins