Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis

Abstract

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2-3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of Journal Articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.

Keywords: Allergic rhinitis; China; diagnosis; treatment.

Fig. 1. Prevalence of adult AR in major cities in China in 2005 and 2011.

Fig. 2. The prevalence of sensitization to dust mites in China.

Fig. 3. Diagnostic flowchart for LAR. AR, allergic rhinitis; SPT, skin prick test; IgE, immunoglobulin E; NPT, nasal provocation test; LAR, local allergic rhinitis; NAR, non-allergic rhinitis; sIgE, serum-specific IgE.

Fig. 4. Susceptibility loci of AR in Chinese population studies. Some loci were reported only in Chinese populations (loci shown in black) or in both Chinese populations and other ethnic populations (loci shown in red).

Fig. 5. The potential effects of miR-143 and miR-135a on signaling pathways. While miR-143 can inhibit the expression of GM-CSF, eotaxin, and MUC5AC by suppressing the IL13Rα1 signalling pathway, miR-135a can down-regulate the mRNA and protein expression levels of GATA-3 and IL-4 and up-regulate the expression levels of T-bet and IFN-γ, thereby correcting the Th1/Th2 imbalance.

Fig. 6. The process of allergen sensitization in AR. Following exposure of nasal mucosa to allergens, allergens are captured, taken up, and processed by dendritic cells (DCs). Subsequently, DCs are activate and, mature, and migrate to regional lymph nodes or to sites in the local mucosa, where they present allergen-derived peptides in the context of MHC class II molecules to naïve T cells. Naïve T cells then differentiate into Th2 cells, which produce IL-4 and IL-13 in the presence of early IL-4. In the presence of these Th2-derived cytokines, together with ligation of the suitable co-stimulatory molecules (CD40 ligand with CD40 and CD28 with CD80), B cells undergo immunoglobulin class-switch recombination to produce IgE antibodies. The locally and/or systemically diffused IgE binds to the high-affinity receptors (FcεRI) on mast cells and basophils (not shown), and results in sensitization of these cells (adapted from Galli and colleagues [142]).

Fig. 7. Early and late phase reactions in AR. (A) Early phase reaction: Ligation of allergen-specific IgE-FcεRI complexes by the corresponding allergen on mast cells activates mast cells to secrete preformed mediators (e.g. histamine and tryptase) and lipid-derived mediators (e.g. PGD2, LTB4 and PAF), which increase vascular permeability, mucus secretion, and blood vessel dilation. This results in watery rhinorrhea, mucosal edema, and nasal congestion. Stimulation of sensory nerves in the nose results in sneezing and sensations of nasal itch and congestion (adapted from Galli and colleagues [142]). (B) Late phase reaction: Ligation of IgE-FcεRI complexes by allergen on mast cells results in release of newly synthesized cytokines, chemokines and growth factors, which contribute to the late phase reaction. Mast cells promote the influx and activation of inflammatory leukocytes (such as neutrophils, eosinophils and T cells) by producing TNF-α, LTB4, IL-5, IL-8, and CCL2. T cells that recognize allergen-derived peptides also release products (e.g. IL-4, IL-13, and IL-9) and contribute to late-phase reactions. IL-4 and IL-13 released by Th2 cells can stimulate mast cells to produce more IgE and induce goblet cell hyperplasia, which results in excess mucus production. The recruited immune cells have some downstream effects. For example, elastase released by neutrophils promotes activation of matrix metalloproteinases and degradation of type III collagen. Basic proteins released by eosinophils can cause epithelial cell damage (adapted from Galli and colleagues [142]).

Fig. 8. Self-amplification mechanisms of mast cell degranulation. IL, interleukin; GM-CSF, granulocyte/macrophage colony-stimulating factor; PAR, protease activated receptor (adapted from He and colleagues [152]).

Fig. 9. Self-amplification mechanisms of mast cell accumulation. IL, interleukin; pMC, pregenitor mast cell; MC, mast cell; SCF, stem cell factor; TNF, tumor necrosis factor; RANTES, regulated upon activation normal T cell expressed and secreted; MCP-1, monocyte chemotactic protein-1; PAF, platelet-activating factor (adapted from He and colleagues [152]).

Fig. 10. The role of ILC2 in AR. Type 2 responses are initiated by allergens that disrupt the epithelial barriers and induce secretion of IL-25, IL-33, and TSLP. IL-25 and IL-33 activate ILC2s to produce the type 2 cytokines IL-5 and IL-13. Epithelial cytokines also activate DCs to induce Th2 responses. Secretion of IL-5 by ILC2s leads to the recruitment and activation of mast cells and eosinophils. The activation of T cells further amplifies the secretion of type 2 cytokines, and the production of IL-4 and IL-13 by T cells leads to the production of IgE by B cells. Together, the responses triggered by secretion of type 2 cytokines from ILC2s and Th2 cells play an important role in inducing allergic inflammation.

Fig. 11. Stimulation of allergen on C fibers may lead to the release of substance P via axon reflex.

Fig. 12. A reprehensive endoscopic image of nasal mucosa suffering from AR.

Fig. 13. Nasal irrigation equipment developed and patented by Beijing Tongren Hospital. (A) Nasal irrigator and salt package. (B) A patient performing nasal irrigation.

Fig. 14. Allergen tolerance: changes in cells of allergic inflammation during allergen tolerance. AIT, allergen-specific immunotherapy; Breg, B regulatory cell; Treg, T regulatory cell.

Fig. 15. SCIT-related local reaction.

Fig. 16. Vidian neurectomy diagram. (A) The area of incision and anatomical surroundings of interest in endoscopic vidian neurectomy. Yellow curved line indicates an incision; the oval, the location of sphenopalatine foramen; and the circle, the location of the pterygoid canal. (B) The yellow arrow indicates the horn-shaped pterygoid canal and nerve. E, indicates ethmoid sinus; IT, inferior turbinate; MT, middle turbinate; SS, sphenoid sinus; NS, nasal septum; PC, posterior choana.

Fig. 17. Acupuncture site. (A) Common acupuncture sites. (B) Site of sphenopalatine ganglion acupuncture for AR. (C) High- resolution CT scan 3-dimensional reconstruction of the sphenopalatine ganglion acupuncture site.