不同严重程度鼻炎患者尘螨舌下特异性免疫治疗临床效果观察

目的　评估不同严重程度变应性鼻炎（allergic rhinitis，AR）患儿进行规范化舌下特异性免疫治疗（sublingual immunotherapy， SLIT）的疗效。方法　选取2017年5—12月首都儿科研究所附属儿童医院耳鼻喉科就诊的3～14岁对粉尘螨过敏的AR患儿181例， 按治疗方式不同分为对照组（n＝92， 给予常规药物治疗）和SLIT组（n＝89， 给予尘螨特异性免疫治疗）； 采用AR评分标准， 根据患儿鼻部症状总评分（total nasal symptoms score， TNSS）， 将对照组分为轻度组（n＝35）、中度组（n＝28）和重度组（n＝29）；将SLIT分为轻度组（n＝27）、中度组（n＝33）和重度组（n＝29）。收集第6个月、 1年、 2年的随访数据， 分别对患儿进行TNSS、 鼻炎用药评分（total rhinitis medication scores， TRMS）和视觉模拟量表（visual analogue scale，VAS）评分。结果　（1）治疗2年后， SLIT组与对照组患儿TNSS评分分别为0.61±0.73、 1.61±1.17， TRMS分别为0.21±0.41、 0.59±0.70， VAS分别为0.63±0.70、 1.53±1.24， 两组间差异有统计学意义， Z值分别为6.269、 4.139、5.174， P值均＜0.05； （2）轻度组（n＝62）组内分析： SLIT组（n＝27）与对照组（n＝35）比较， 治疗6个月、 1年， 两组的TNSS、 TRMS、 VAS差异均无统计学意义（Z值分别为-0.108、 0.232、 0.788， 0.774、 0.033、 -0.718； P值均＞0.05）； 治疗2年时两组的TRMS、 VAS差异无统计学意义（Z值分别为0.230、 1.255， P＞0.05）， TNSS在两组间差异有统计学意义（Z值为2.528， P值均＜0.05）； （3）中度组（n＝61）组内分析： 与对照组（n＝28）比较， SLIT组（n＝33）治疗6个月， TRMS、 VAS在两组间差异均无统计学意义（Z值分别为-0.413、 0.412， P值均＞0.05）， 但两组的TNSS差异有统计学意义（Z值为2.397， P＜0.05）； 治疗1年、2年的TNSS、 TRMS、 VAS两组间比较， 差异均有统计学意义（Z值分别为4.952、 2.740、 3.293； 4.743、 2.505、 3.330； P值均＜0.05）； （4）重度组（n＝58）组内分析： 与对照组（n＝29）比较， SLIT组（n＝29）治疗6个月、 1年、 2年的TNSS、 TRMS、 VAS在两组间差异均有统计学意义（Z值分别为2.567、 2.086、 2.781， 4.996、 4.264、 2.756， 4.253、 4.480、 4.515， P值均＜0.05）。结论　采用标准化粉尘螨滴剂舌下治疗尘螨致敏AR患儿， 治疗2年可获得较单纯药物治疗更佳的疗效， 尤其在病情严重患儿，其获益更大。     

Current therapeutical strategies for allergic rhinitis

Introduction: Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option.

Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies.

Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.     

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

Skin test results and self-reported symptom severity in allergic rhinitis: the role of psychological factors

BACKGROUND: In allergic conditions, the degree of skin test reactivity does not always correlate with the severity of clinical symptoms. Additional factors may contribute to the reported symptom severity. OBJECTIVES: To investigate the association between the magnitude of the skin prick test (SPT) response and the reported symptom severity in patients with allergic rhinitis and the possible modifying role of psychological factors. METHODS: One hundred four patients with allergic rhinitis and 23 with non-allergic rhinitis, classified according to their SPT response to 19 aeroallergens, were asked to rate the severity of five symptoms and to indicate whether their symptoms intensified on exposure to five common aeroallergens. They also completed a psychological questionnaire. Results Reported symptom severity of allergic rhinitis did not correlate with weal size for any of the aeroallergens tested or with the number of positive responses on SPT. It was not related to patient age, sex, or education. The reported symptoms severity correlated positively (0.29, P < 0.01) with reported symptom intensification on exposure to allergens. Moreover, both outcomes were positively associated with the psychological factors of hypochondriasis (0.20, P < 0.05 and 0.18, P < 0.05, respectively), and somatic awareness (0.24, P < 0.05 and 0.33, P < 0.01, respectively), but not with neuroticism. CONCLUSIONS: The severity of symptoms experienced by patients with allergic rhinitis is apparently not related to the magnitude of SPT response, but rather to psychological factors of hypochondriasis and somatic awareness. Physicians should be aware of the contribution of psychological factors to patient perceptions of the intensity of symptoms and of the intensification of symptoms on their exposure to allergens.     

Local mucosal immunoglobulin E production: does allergy exist in non‐allergic rhinitis?

In this review, we critically evaluate the evidence for local IgE production in allergic rhinitis mucosa and the concept of local allergy in non-atopic idiopathic rhinitis. Significantly, fewer studies have focused on the disease pathways associated with non-allergic rhinitis compared with their allergic counterparts. Recently, there's been a revival of the hypothesis concerning the existence of local tissue-specific allergic disease confined to the nasal mucosa of some systemically non-atopic rhinitis subjects. Providing the evidence for local mucosal IgE production in allergic rhinitis is a pre-requisite to reviewing its existence in non-allergic rhinitis. In addition, practical and theoretical approaches useful in the detection of allergy in non-allergic rhinitis will be discussed. Furthermore, successful therapeutic regimens used in the treatment of non-allergic rhinitis will be examined as these could provide an insight into the underlying pathophysiology of this common but poorly understood disease.     

TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.     

Sensitization to Zygophyllum fabago pollen. A clinical and immunologic study

Zygophyllum fahago is a herbaceous plant found widely in the Mediterranean area. There are no previous reports of its allergenicity. An aerobiologic and clinical survey was conducted in Murcia, southern Spain, to determine the quantity of airborne pollen and establish the possible role of this pollen as a cause of allergic symptoms. With a Hirst volumetric trap, we determined the atmospheric concentrations of this pollen in 1993, 1994,1995, and 1996. Of 1180 patients tested, 181 (15,34%) had a positive skin test. To determine its allergenicity, we divided 47 patients into three groups: in group 1, all the patients had symptoms of rhinoconjunctivitis plus asthma; in groups 2 and 3, rhinoconjunctivitis. In group 1, we performed a bronchial provocation test (BPT): in groups 2 and 3, we performed nasal provocation (NPT) and conjunctival provocation (CPT) tests, respectively, SDS-PAGE was used to characterize the antigenic fractions and RAST inhibition to determine cross-reactivity with other pollens. The pollen dispersion period is from May to September (445 grains/m³), BPT was positive in 13 of 15 patients, NPT in 14 of 16 patients, and CPT in 13 of 16 patients. RAST inhibition revealed cross-reactivity with Mercurialis, Ricinus, Olea. and Betula. SDS-PAGE identified 25 IgE antibody-binding components, five of which (60, 65, 41, 38, and 15.5/14,7 kDa) were recognized by 40% of the sera. By SDS-PAGE immunoblotting with sunflower antiprofilin rabbit serum and affinity chromatography we established that the Z. fahago extract has profilin. This study shows that this pollen becomes airborne and elicits an IgE response which triggers respiratory symptoms in allergic subjects.     

Acoustic rhinometry in nasal provocation test in perennial allergic rhinitis

Acoustic rhinometry is one method to evaluate nasal geometry by an acoustic reflection technique. The aim of this study was to investigate the changes in acoustic rhinometry after nasal provocation in patients with exclusively perennial allergic rhinitis. In 19 patients, acoustic rhinometry and active anterior rhinomanometry were performed before and after nasal provocation test. There was a statistically significant nasal flow reduction measured by active anterior rhinomanometry after nasal provocation (p < 0.05) and a median symptom score of four points, both indicating a positive response to nasal provocation. On the other hand, there was no statistically significant change in the values of acoustic rhinometry after nasal provocation (p > 0.05). In patients with exclusively perennial allergic rhinitis, acoustic rhinometry does not seem to significantly change after nasal provocation. In contrast, active anterior rhinomanometry values decreased significantly after nasal provocation. The presented results indicate that acoustic rhinometry does not seem to be a diagnostic method superior to active anterior rhinomanometry in this context.