Figures
- FIGURE 1
Microphotographs (×20) of endobronchial biopsies from a) healthy control, b) mildly asthmatic and c) severe asthmatic airways demonstrating increased thickness of the basement membrane (haematoxylin–eosin stain) and goblet cell (GC) hyperplasia (periodic acid–Schiff stain) as asthma severity increases. EP: epithelium; RBMt: reticular basement membrane; Ang: angiogenesis. Scale bars=50 μm.
Tables
- TABLE 1
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.] 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.
