Severe Asthma: An Expanding and Mounting Clinical Challenge

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Severe Asthma: An Expanding and Mounting Clinical Challenge Matthew C. Bell, MD, William W. Busse, MD  The Journal of Allergy and Clinical Immunology: In Practice  Volume 1, Issue 2, Pages 110-121 (March 2013) DOI: 10.1016/j.jaip.2013.01.005 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 1 Inflammatory and remodeling responses in asthma with activation of the epithelial mesenchymal trophic unit. Epithelial damage alters the set point for communication between bronchial epithelium and underlying mesenchymal cells, leading to myofibroblast activation, an increase in mesenchymal volume, and induction of structural changes throughout airway wall. Adapted from Davies et al18 and from Holgate and Polosa.23 The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 110-121DOI: (10.1016/j.jaip.2013.01.005) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 2 Relative change in FEV1 in the intention-to-treat population. A, At week 12, the increase from baseline in FEV1 was higher by 5.5 percentage points (95% CI, 0.8-10.2 percentage points) in the lebrikizumab group than in the placebo group (mean ± SE change, 9.8% ± 1.9% vs 4.3% ± 1.5%; P = .02). B, In the subgroup of patients with high periostin levels (high TH2), the relative increase from baseline FEV1 was higher by 8.2 percentage points (95% CI, 1.0-15.4 percentage points) in the lebrikizumab group than in the placebo group (mean change, 14.0% ± 3.1% vs 5.8% ± 2.1%; P = .03). C, Among patients in the low-periostin subgroup (low TH2), the relative increase from baseline FEV1 was higher by 1.6 percentage points (95% CI, −4.5 to 7.7 percentage points) in the lebrikizumab group than in the placebo group (mean change, 5.1% ± 2.4% vs 3.5% ± 2.1%; P = .61). Reprinted from Corren et al.50 The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 110-121DOI: (10.1016/j.jaip.2013.01.005) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 3 Health care utilization events during the posttreatment period. Severe exacerbations (exacerbation requiring treatment with systemic corticosteroids or doubling of the inhaled corticosteroids dose), emergency department visits, and hospitalizations occurring in the posttreatment period. Open bars, sham; shaded bars, bronchial thermoplasty. All values are means ± SEMs. ∗P < .05. †P < .01. Reprinted from Castro et al.53 The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 110-121DOI: (10.1016/j.jaip.2013.01.005) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 4 Personalized treatment algorithm for patients with difficult-to-control asthma. ABP, allergic bronchopulmonary aspergillosis; CF, cystic fibrosis; PPI, proton pump inhibitor. The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 110-121DOI: (10.1016/j.jaip.2013.01.005) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions