Perhaps the results that now have come up repeatedly suggest, then, something that we all know: do not screen populations not known to be at an elevated risk. Testing only HCWs and other persons known to have been exposed to a case of transmissible TB would by definition almost entirely remove the problem, unnecessary anxiety among those concerned, and also entail substantial cost savings. Perhaps such a bottom-line approach would prove more useful in the long run than fiddling around with fine- tuning cutoff points. Indeed, we need to rethink whether it is really justifiable to subject HCWs in low-incidence countries to annual testing, even if their risk of infection is likely (if probably only marginally so) higher than that of the general population. Infection control measures are highly effective in decreasing the risk of infection among HCWs (13, 14). Notably, not a single HCW in this study nor in that by Slater and colleagues (2) developed TB during the observation period. On the other side, in respect to the very high risk of infection (15) and disease (16) in HCWs employed in settings where infection control measures are insufficient, one must ask if a reallocation of resources to more cost-effective actions than annual testing of HCWs would not be indicated. n Author disclosures are available with the text of this article at www. atsjournals.org. Jean-Pierre Zellweger, M.D. TB Competence Center Swiss Lung Association Berne, Switzerland Hans L. Rieder, M.D., M.P.H. International Union against Tuberculosis and Lung Disease (The Union) Paris, France and University of Zurich Zurich, Switzerland References 1. Dorman SE, Belknap R, Graviss EA, Reves R, Schluger N, Weinfurter P, Wang Y, Cronin W, Hirsch-Moverman Y, Teeter LD, et al.; for the Tuberculosis Epidemiologic Studies Consortium. Interferon-g release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. Am J Respir Crit Care Med 2014;189:77–87. 2. Slater ML, Welland G, Pai M, Parsonnet J, Banaei N. Challenges with QuantiFERON-TB Gold assay for large-scale, routine screening of U.S. healthcare workers. Am J Respir Crit Care Med 2013;188:1005–1010. 3. Zwerling A, Cojocariu M, McIntosh F, Pietrangelo F, Behr MA, Schwartzman K, Benedetti A, Dendukuri N, Menzies D, Pai M. TB screening in Canadian health care workers using interferon-gamma release assays. PLoS ONE 2012;7:e43014. 4. Zwerling A, van den Hof S, Scholten J, Cobelens F, Menzies D, Pai M. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax 2012;67:62–70. 5. Moucaut A, Nienhaus A, Courtois B, Nael V, Longuenesse C, Ripault B, Rucay P, Moisan S, Roquelaure Y, Tripodi D. The effect of introducing IGRA to screen French healthcare workers for tuberculosis and potential conclusions for the work organisation. J Occup Med Toxicol 2013;8:12. 6. Gran G, Aßmus J, Dyrhol-Riise AM. Screening for latent tuberculosis in Norwegian health care workers: high frequency of discordant tuberculin skin test positive and interferon-gamma release assay negative results. BMC Public Health 2013;13:353. 7. Nienhaus A, Ringshausen FC, Costa JT, Schablon A, Tripodi D. IFN-g release assay versus tuberculin skin test for monitoring TB infection in healthcare workers. Expert Rev Anti Infect Ther 2013;11:37–48. 8. Stebler A, Iseli P, M ¨ uhlemann K, Bodmer T. Whole-blood interferon- gamma release assay for baseline tuberculosis screening of healthcare workers at a Swiss university hospital. Infect Control Hosp Epidemiol 2008;29:681–683. 9. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K; IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep 2010;59:1–25. 10. Loddenkemper R, Diel R, Nienhaus A. To repeat or not to repeat-that is the question!: Serial testing of health-care workers for TB infection. Chest 2012;142:10–11. 11. Thanassi W, Noda A, Hernandez B, Newell J, Terpeluk P, Marder D, Yesavage JA. Delineating a retesting zone using receiver operating characteristic analysis on serial QuantiFERON Tuberculosis test results in US healthcare workers. Pulm Med 2012;2012:291294. 12. Nienhaus A, Costa JT. Screening for tuberculosis and the use of a borderline zone for the interpretation of the interferon-g release assay (IGRA) in Portuguese healthcare workers. J Occup Med Toxicol 2013;8:1. 13. Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and disease associated with work in health care settings. Int J Tuberc Lung Dis 2007;11:593–605. 14. Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005;54:1–141. 15. Drobniewski F, Balabanova Y, Zakamova E, Nikolayevskyy V, Fedorin I. Rates of latent tuberculosis in health care staff in Russia. PLoS Med 2007;4:e55. 16. Baussano I, Nunn P, Williams B, Pivetta E, Bugiani M, Scano F. Tuberculosis among health care workers. Emerg Infect Dis 2011;17: 488–494. Copyright © 2014 by the American Thoracic Society IL-4Ra, a STUB-strate for Proteasomal Degradation: Understanding the Termination of Cytokine Signaling in Asthma The IL-4/IL-13 cytokine network has consistently been implicated in the pathogenesis of allergic asthma (1). The heterodimeric receptors for IL-4 and IL-13 share a common subunit, the IL-4 receptor a (IL-4Ra), which is responsible for signal transduction upon cytokine binding. The combined blockade of IL-4 and IL-13 by treatment with a soluble IL-4 receptor has shown promise in alleviating symptoms in patients with asthma (2, 3), and polymorphisms in genes involved in this pathway are also associated with asthma (4). Although susceptibility to asthma is clearly a complex phenomenon and influenced by Author Contributions: K.Y. and B.J.M. wrote this editorial. K.Y. generated the figure. EDITORIALS 4 American Journal of Respiratory and Critical Care Medicine Volume 189 Number 1 | January 2014