The missing environmental factor in celiac disease.

n engl j med 371;14 nejm.org october 2, 2014 1341 States, the reported retail cost of fluticasone at 500 μg per day (half the dose used in this study) is $194 per month.10 The investigators report a hazard ratio for exacerbations of 1.05 among patients who stopped taking glucocorticoids, as compared with those who continued the glucocorticoid regimen. The upper bound of the confidence interval was within the prespecified range of noninferiority for glucocorticoid withdrawal. Similar results were seen in a variety of subgroup analyses and support the hypothesis that the withdrawal of glucocorticoids in patients receiving therapy with LABAs and LAMAs does not result in an increased risk of exacerbation. Patients in the glucocorticoid-withdrawal group had small reductions in the FEV1 and in measures of health-related quality of life, although the clinical importance of these changes is not clear. As the authors state, the trial leaves some questions unanswered. Is it necessary to taper the glucocorticoid dose or could one-step withdrawal provide the same results? Is a period of 6 weeks of maximal therapy required before glucocorticoid withdrawal? The results of this trial, taken together with the findings of other studies, suggest that the rationale for continuing glucocorticoid therapy in patients who are also taking long-acting bronchodilators should be based on symptomatic improvement attributable to the glucocorticoid rather on the prevention of exacerbations. They also show that a trial of glucocorticoid withdrawal will not increase the risk of exacerbation, even in patients with severe COPD. The findings may prompt clinicians to consider other preventive interventions, such as daily azithromycin, in patients who continue to have frequent exacerbations while receiving long-acting bronchodilators.11 Disclosure forms provided by the author are available with the full text of this article at NEJM.org.