The main findings of important recent clinical and experimental studies directly associating IgE or anti-IgE treatment with features of airway remodelling

First author [ref.]YearStudy designMain findings
Gounni [30]2005Experimental study In vitro (HASM cells from atopic  asthmatics, n=6)HASM cells express FcεRI (high-affinity IgE receptor) IgE stimulation triggered HASM contraction and IL-4,  IL-5, IL-13 and eotaxin release
Kang [70]2010Experimental study Murine model of chronic asthma Three groups (control, OVA and  omalizumab + OVA)Omalizumab decreased airway hyperresponsiveness, BALF inflammatory cell counts, BALF IL-5 and IL-13  levels, peribronchial collagen III/V, hydroxyproline  and α-smooth muscle actin BALF TGF-β and activin-A levels were not significantly  altered in the omalizumab group (although both  tended to increase)
Roth [31]2010Experimental study In vitro (primary HASM cells) Three groups (allergic asthma, COPD  and control, n=6 each)IgE stimulation increased IL-6, IL-8 and TNF-α mRNA  synthesis and secretion by HASM cells in all groups Omalizumab inhibited IgE-stimulated cytokine secretion  in a dose-dependent fashion
Riccio [64]2012Clinical study 11 severely allergic asthmatics 1 year omalizumabSignificant reduction in RBM thickness in bronchial  biopsies Reduction of the number of infiltrating eosinophils  (not significant)
Hoshino [65]2012Clinical study 30 severely allergic asthmatics Randomised 1:1 (omalizumab versus  conventional therapy for 16 weeks)Omalizumab decreased WA/BSA, WA percentage and T/√BSA and increased Ai/BSA as assessed by computed  tomography Omalizumab decreased percentage of sputum  eosinophils and increased FEV1 and AQLQ scores Changes in FEV1 and sputum eosinophils correlated with  changes in WA percentage
Roth [32]2013Experimental study In vitro (primary HASM cells) Two groups (allergic asthmatics and  nonasthmatics, both n=8)IgE increased HASM cell proliferation and extracellular  matrix and collagen deposition in a dose-dependent  manner IgE effects were more prominent in asthmatic tissue Pre-incubation with omalizumab prevented all  remodelling effects
Redhu [33]2013Experimental study In vitro (primary HASM)IgE-induced proliferation of HASM cells via MAPK,  Akt and STAT3 signalling pathways
Mauri [72]2014Clinical study Severely allergic asthmatics (n=8) 1 year omalizumab Proteomics of bronchial biopsiesOmalizumab downregulated bronchial smooth muscle  proteins Among extracellular matrix proteins, galectin-3  correlated best with airway remodelling modulation  by omalizumab
Tajiri [66]2014Clinical study 31 severely allergic asthmatics 48 weeks omalizumab  (assessment at baseline,  16 and 48 weeks)Omalizumab decreased WA percentage and thickness  and increased Ai and Ai/BSA as assessed by  computed tomography WA percentage changes significantly correlated with  the decrease in FeNO50 levels and sputum eosinophils
  • HASM: human airway smooth muscle; IL: interleukin; OVA: ovalbumin; BALF: bronchoalveolar lavage fluid; TGF: transforming growth factor; COPD: chronic obstructive pulmonary diesase; TNF: tumour necrosis factor; RBM: reticular basement membrane; WA: wall area; BSA: body surface area; T/√BSA: wall thickness; Ai: luminal area at the right apical segmental bronchus; FEV1: forced expiratory volume in 1 s; AQLQ: asthma quality of life questionnaire; MAPK: mitogen-activated protein kinase; STAT: signal transducer and activator of transcription; FeNO50: exhaled nitric oxide fraction at 50 mL·s-1.