T h e NEW ENGLAND JOUR NAL o f MEDICINE N ENGL J MED 365;25 NEJM.ORG DECEMBER 22, 2011 Corren et al. (Sept. 22 issue)1 report that treatment with lebrikizumab was associated with improved lung function in patients with asthma, and that improvement wasgreater in patients with high pretreatment levels of serum periostin or of the fraction of exhaled nitric oxide (FENO). The authors justifiably emphasize periostin because of its lower intra-patient variability, but in doing so, they raise an important question: what is the relationship between periostin and FENO at baseline in individual patients? After 12 weeks of lebrikizumab therapy, forced expiratory volume in 1 second (FEV1) improved by 8.6 percentage points in the group with high FENO levels, as compared with placebo (P?=?0.02), and by 8.2 percentage points in the group with high periostin levels, as compared with placebo (P?=?0.03). At 24 weeks, improvement in FEV1 was 40% greater in the FENO-high group than in the periostin-high group (5.9% vs. 4.2%) (P?=?0.09 in the FENO-high group and P?=?0.26 in the periostin-high group for the comparison of lebrikizumab with placebo) (see Table S4 in the Supplementary Appendix, available with the full text of the article by Corren et al. at NEJM.org). These data suggest that some patients who have both low-periostin levels and high FENO levels may benefit from lebrikizumab treatment as much as patients in the periostin-high group do. If so, this would increase the number of patients considered likely to respond to lebrikizumab. Investigating the re-lationship between periostin and FENO may also provide insight into the mechanism of action of lebrikizumab. All Author: Benjamin Zeskind, Ph.D.