title: Comprehensive efficacy of omalizumab for severe refractory asthma: a time-series observational study.
abstract: BACKGROUND
  Omalizumab, a humanized anti-IgE monoclonal antibody, is reportedly an effective treatment for severe allergic asthma. However, there have been few comprehensive analyses of its efficacy, including assessments of small airways or airway remodeling.
  
  
  OBJECTIVE
  To comprehensively evaluate the efficacy of omalizumab, including its effects on small airways and airway remodeling, in adult patients with severe refractory asthma.
  
  
  METHODS
  In this prospective, time-series, single-arm observational study, 31 adult patients with severe refractory asthma despite the use of multiple controller medications, including high-dose inhaled corticosteroids (1,432 ± 581 μg/d of fluticasone propionate equivalent), were enrolled. Clinical variables, including Asthma Quality of Life Questionnaire, asthma exacerbations, exhaled nitric oxide, pulmonary function, methacholine airway responsiveness, induced sputum, and chest computed tomogram, were assessed at baseline and after 16 and 48 weeks of treatment with omalizumab.
  
  
  RESULTS
  Twenty-six of the 31 patients completed 48 weeks of treatment. For these patients, Asthma Quality of Life Questionnaire scores and peak expiratory flow values significantly and continuously improved throughout the 48 weeks (P < .001 for all comparisons). Unscheduled physician visits, asthma exacerbations requiring systemic corticosteroids, fractional exhaled nitric oxide at 50 mL/s and alveolar nitric oxide levels, sputum eosinophil proportions, and airway-wall thickness as assessed by computed tomography significantly decreased at 48 weeks (P < .05 for all comparisons).
  
  
  CONCLUSIONS
  Omalizumab was effective for adult patients with severe refractory asthma. Omalizumab may have anti-inflammatory effects on small airways and reverse airway remodeling.
  
  
  BACKGROUND
  UMIN000002389.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Division of Respiratory Medicine, Department of Medical Oncology and Immunology, Nagoya City University School of Medical Sciences, Aichi, Japan. Electronic address: a.niimi@med.nagoya-cu.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakaji
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Nagasaki
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Izuhara
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D000069444:Omalizumab; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011446:Prospective Studies; D011788:Quality of Life; D012129:Respiratory Function Tests; D013183:Sputum / Q000737:chemistry; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D016210:Methacholine Chloride; D000069444:Omalizumab; D009569:Nitric Oxide; D007073:Immunoglobulin E