RT Journal A1 Chan CM, Shorr AF T1 Black clouds and black boxes: Comment on “long-acting β2-agonist step-off in patients with controlled asthma” JF Archives of Internal Medicine JO Archives of Internal Medicine YR 2012 FD October 8 VO 172 IS 18 SP 1375 OP 1376 DO 10.1001/archinternmed.2012.3650 UL http://dx.doi.org/10.1001/archinternmed.2012.3650 AB For more than a decade, black clouds have surrounded the safety of long-acting β2-agonists (LABAs) for asthma. Several studies1- 2 indicate that these agents are associated with an increased risk for asthma-related morbidity and mortality. Although these trials were flawed and the absolute increase in mortality risk with LABAs was small, it persisted in multiple analyses. Thus, there is consensus that these agents have no role as monotherapy in asthma.3 Qualms remain, however, about their use in combination with inhaled corticosteroids (ICSs).4 Despite performing their own meta-analysis illustrating that coadministration of ICSs and LABAs essentially eliminated the enhanced risk related to LABA exposure, the US Food and Drug Administration (FDA) instituted a black box warning on LABAs.5 The warning states that LABAs, when given with ICSs, should be discontinued as soon as asthma control is achieved. The authors of the third Expert Panel Report of the National Asthma Education and Prevention Program guidelines3 interpreted the data differently and did not endorse such an approach. With more than 25 million Americans having asthma, clinicians are left facing the quandary of how to manage these patients, many of whom receive suboptimal control with ICSs alone.6