First author [ref.] | Year | Study design | Main findings |
Gounni [30] | 2005 | Experimental 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] | 2010 | Experimental 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] | 2010 | Experimental 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] | 2012 | Clinical study 11 severely allergic asthmatics 1 year omalizumab | Significant reduction in RBM thickness in bronchial biopsies Reduction of the number of infiltrating eosinophils (not significant) |
Hoshino [65] | 2012 | Clinical 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] | 2013 | Experimental 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] | 2013 | Experimental study In vitro (primary HASM) | IgE-induced proliferation of HASM cells via MAPK, Akt and STAT3 signalling pathways |
Mauri [72] | 2014 | Clinical study Severely allergic asthmatics (n=8) 1 year omalizumab Proteomics of bronchial biopsies | Omalizumab downregulated bronchial smooth muscle proteins Among extracellular matrix proteins, galectin-3 correlated best with airway remodelling modulation by omalizumab |
Tajiri [66] | 2014 | Clinical 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.