Objective. To evaluate the association of glucocorticoids and other purported risk factors with the development of tuberculosis. Methods. We conducted a case-control study of tuberculosis cases identified during 1990 -2001 using the General Practice Research Database in the United Kingdom. Cases were patients with a first time diagnosis of tuberculosis accompanied by at least 6 months of treatment with at least 3 different tuberculosis medications. Up to 4 controls were matched to each case on age, sex, the practice attended by the case, index date, and amount of prior computerized records. Results. The study encompassed 497 new cases of tuberculosis and 1,966 controls derived from 16,629,041 person-years at risk (n ‫؍‬ 2,757,084 persons). The adjusted odds ratio (OR) of tuberculosis for current use of a glucocorticoid compared with no use was 4.9 (95% confidence interval [95% CI] 2.9 -8.3). The adjusted ORs for use of <15 mg and >15 mg of prednisone or its equivalent daily dose were 2.8 (95% CI 1.0 -7.9) and 7.7 (95% CI 2.8 -21.4), respectively. Adjusted ORs of tuberculosis were 2.8 for patients with a body mass index (BMI) <20 compared with normal BMI; 1.6 for current smokers compared with nonsmokers; and 3.8, 3.2, 2.0, and 1.4 for those with history of diabetes, emphysema, bronchitis, and asthma, respectively, compared with those without such history (all P values <0.05). Conclusion. These results indicate that patients treated with glucocorticoids have an increased risk of developing tuberculosis, independent of other risk factors. Low adiposity, diabetes, current smoking, and obstructive pulmonary disorders are also important independent risk factors for tuberculosis.

essential for the growth of some neoplastic cells including melanoma and hepatocellular carcinoma among others.Where does this leave us and what does all this have to do with the study by Vadillo-Ortega et al? First and most importantly, the balance between the protective and adverse effects of NO seems to be determined by the relative amount of NO and reactive radicals, yet the effects of these vary by tissue in ways not well understood. Second, a relative L-arginine deficiency does uncouple NOS and arginase pathways. Arginase upregulation seems to dominate during L-arginine deficiency resulting in NO deficiency and enhanced production of reactive oxygen species by NOS. Peroxynitrite is formed in place of NO and this leads to microvascular damage and impairs cytotrophoblast invasion. In contrast, the angiogenic/vasculogenic properties of NO likely promote cytotrophoblast endovascular invasion of uterine spiral arterials. Vadillo-Ortega et al attacked this NO deficiency by increasing the substrate through dietary arginine and seemed to demonstrate a beneficial effect, which likely would have resulted from recoupling of the NOS and arginase pathways. That being said, arginine supplementation may be a shotgun approach to what needs to be a sniper shot and therefore could well be associated with significant collateral damage since excessive NO production is not necessarily benign. Recent studies would suggest that a better approach would include both prevention of arginine deficiency but also suppression of the upregulation of arginase. As yet, however, specific ways to block arginase are awaiting discovery. As stated by Braam and Vehaar (Curr Pharm Des 2007;13:1727-1740, "Ideally, eNOS is sufficiently expressed, produces NO sufficiently and not abundantly, does not produce superoxide and is not scavenged by ROS; the produced NO then reaches its signaling target, mainly soluble guanylyl cyclase (sGC) and elicits a cellular responsey there is a great challenge ahead."