儿童过敏性鼻炎的特异性免疫治疗

特异性免疫治疗（AIT）是目前惟一可能改变儿童过敏性鼻炎（AR）自然病程的治疗方法,在取得了良好临床疗效的同时减少了AR患儿的药物用量,提高了生活质量。预防AR进展到哮喘,并减少新的变应原过敏。针对AIT产生的新方法、新技术的目的是缩短达到免疫耐受的时间,提高患儿依从性,增强治疗的安全性,并尽可能的降低治疗负担。该文对AR患儿AIT临床进展进行综述。     

Cytokines in nasal fluids from school children with seasonal allergic rhinitis

Allergic rhinitis is a particularly good model for studies of cytokine pro-duction in vivo , in this study the occurrence of the cytokines IL-4, IL-5. IL-10 and IFN-yas well as the soluble receptor tbr IL-4 in nasal lavage flu-ids were assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy age matched, non atopic controls, using highly sensitive enzyme immunossays. IL-4 levels in patients with seasonal allergie rhinitis were markedly increased in comparison with those in non-atopic controls or in atopic pa-tients before the start of the pollen season. In controls, but not in the atopic patients, levels of IFN-yand IL-5 were significantly higher in specimens obtained during the pollen season than in those obtained outside the season. The IL-4/IFN-y ratios were significantly higher in atopic than in nonalopic subjects and further increased in atopic patients during the season. In addition to IL-4, elevated levels of IL-10 were observed in association with seasonal rhinitis. Following treatment with a topical steroid (budeso nide) there was a statistically significant increase of the levels of soluble IL-4 receptor. These findings indicate that nonatopic and atopic individuals react to pollen exposure with distinct cytokine patterns in agreement with the Thl/ Th2 concept. Topical steroids may possibly decrease inflammation by increasing the formation of soluble IL-4 receptor.     

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.     

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目的 探讨特异性免疫治疗变应性哮喘合并鼻炎的效果,分析特异性免疫治疗期间病情反复的原因。方法 将上海交通大学医学院附属新华医院2006年1月至2010年12月期间收治的102例变应性哮喘合并鼻炎的患儿,分为治疗组和对照组,治疗组78例在哮喘规范化防治基础上联合粉尘螨注射液特异性免疫治疗,而对照组24例以吸入激素等规范化防治为主。评价两组患儿治疗6个月、1年、2年及治疗结束后随访1年哮喘最大呼气流量(PEF)、汉化版儿童哮喘控制测试量表(Ch-CACT)结果和变应性鼻炎的临床症状评分及视觉模拟评分(VAS),比较两组患儿治疗第2年及治疗结束后随访1年哮喘急性发作次数和呼吸道感染情况,并分析特异性免疫治疗期间病情反复的原因。结果 治疗第2年及治疗结束后随访1年哮喘急性发作次数和呼吸道感染次数均较对照组减少,差异具有统计学意义(P<0.01)。治疗组治疗2年及治疗结束后随访1年哮喘PEF测定结果优于对照组,治疗结束后随访1年Ch-CACT较对照组高,差异均具有统计学意义(P<0.05)。治疗6个月、1年、2年及治疗结束后随访1年治疗组变应性鼻炎的临床症状评分和VAS评分优于对照组,差异具有统计学意义(P<0.05)。特异性免疫治疗期间导致病情反复的常见原因为气候因素、呼吸道感染、合并副鼻窦炎及不适当的居室清扫等。结论 特异性免疫治疗能改善哮喘患儿的PEF及Ch-CACT评分,能明显改善变应性鼻炎的临床症状及VAS评分,是一种防治变应性哮喘合并鼻炎持久有效的方法。气候因素、呼吸道感染及合并副鼻窦炎是导致特异性免疫治疗期间病情反复的主要原因。     

北京地区学龄儿童变应性鼻炎相关因素分析

目的 了解北京城区学龄儿童变应性鼻炎的主要变应原、伴发结膜炎的情况及其与气道高反应的关系.方法 2006年和2007年8-9月在首都儿科研究所耳鼻喉科门诊就诊的100例6～14岁的变应性鼻炎患儿为病例组,小学健康儿童(无变态反应性疾病)30名为正常对照组,进行问卷调查及吸入变应原皮肤点刺试验(skin prick test,SPT);随机选取病例组中53例鼻炎患儿和对照组30名儿童做乙酰甲胆碱气道激发试验(methacholine bronchial provocation test,Mth BPT).结果 ①变应性鼻炎组中螨、霉菌、艾蒿、猫狗毛、夏秋季花粉、葎草SPT阳性率较高,分别为55%、39%、36%、34%、31%、27%、22%.②变应性鼻炎组中各年龄组螨SPT阳性率差异无统计学意义,而艾蒿和夏秋季花粉随年龄增加SPT阳性率明显增JJ玎(x2=7.51,6.29,P均＜0.05).③变应性鼻炎合并结膜炎患儿为65%.合并结膜炎组患儿变应原阳性数量高于单纯变应件鼻炎组,差异有统计学意义(t=3.06,P＜0.05).④变应性鼻炎症状越重,变应原阳性数幂越多(r=0.21,P=0.04),越可能合并变应件结膜炎(r=0.31,P=0.002).⑤变应性鼻炎组53例患儿乙酰甲且日碱气道激发试验阳性率为77%,正常对照组儿童为16.7%,两组差异有统计学意义(x2=28.56,P＜0.0001).变应性鼻炎组激发试验阳性的发生概率是正常对照组的17.08倍(95%可信区间5.38～54.26).结论 北京城区儿童8-9月变应性鼻炎就诊高峰和花粉变应原有关,其中艾蒿、夏秋季花粉和年龄有相关性.变应性鼻炎合并结膜炎发病率高,应注重结膜炎的诊断和治疗.变应性鼻炎儿童气道反应性增加,应对其积极治疗,减缓和预防哮喘的发生.     

Bet v 1-specific IgA increases during the pollen season but not after a single allergen challenge in children with birch pollen-induced intermittent allergic rhinitis

Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been found in the nasal fluid of patients with allergic rhinitis. IgA may play a protective role, but there are also data which show that allergen-specific IgA can induce eosinophil degranulation. The aim of this study was to quantitate Bet v 1-specific IgA in relation to total IgA in the nasal fluid of children with birch pollen-induced intermittent allergic rhinitis and healthy controls, after allergen challenge and during the natural pollen season. Eosinophil cationic protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 healthy controls. Samples were taken before the pollen season, after challenge with birch pollen and during the pollen season, before and after treatment with nasal steroids. During the pollen season, but not after nasal allergen challenge, Bet v 1-specific IgA increased in relation to total IgA in children with allergic rhinitis. No change was found in the healthy controls. The ratio of Bet v 1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in the allergic children, p < 0.001. No change was seen after treatment with nasal steroids, although symptoms, ECP and eosinophils were reduced. In conclusion, allergen-specific IgA in relation to total IgA increases in nasal fluids during the pollen season in allergic children but not in healthy controls. These findings are compatible with the hypothesis that allergen-specific IgA plays a role in the allergic inflammation and further studies are needed to clarify the functional role of these allergen-specific antibodies.     

Sublingual immunotherapy in children with allergic rhinitis: quality of systematic reviews

Systematic reviews have gained popularity as a way to combine the increasing amount of research information. This study assessed the quality of systematic reviews and meta-analyses of sublingual immunotherapy (SLIT) for allergic rhinitis in children, published since 2000. Eligible reviews were identified by searching Medline/Pubmed, Embase, and the Cochrane Library, from 2000 through 2008. Methodological quality was assessed using the assessment of multiple systematic reviews instrument. Ten systematic reviews were included, one of which was published in the Cochrane Library. Eight reviews gave some details about the search strategy. None of the reviews included measures to avoid selection bias. In 60% of the reviews, the methodological quality of the included studies was (partly) assessed. Four reviews pooled the results of individual studies, neglecting clinical heterogeneity. Three of the 10 reviews provided information about sources of funding or grants from industry. Of the 10 reviews, the six reviews with the highest overall score scored 5-8 points, indicating moderate quality. Systematic reviews are useful to evaluate the efficacy of SLIT in children. Although more reviews have become available, the methodological quality could be improved. SLIT for children could be promising, but methodological flaws in the reviews and individual studies are too serious to draw definite conclusions.     

Nasal hemophilic pseudotumor in a patient with mild hemophilia A and allergic rhinitis

Hemophilic pseudotumor is a rare complication, even in patients with severe hemophilia. Herein we report on a case of hemophilic pseudotumor in a patient with mild hemophilia A and allergic rhinitis, initially suspected to be a nasal tumor. The pseudotumor was cured by supplementation with recombinant factor VIII concentrates, and medication for allergic rhinitis. Pseudotumor should always be considered in hemophiliac patients, even in those with only mild deficiency of coagulation factors.     

Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: A randomized study

Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis-related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three-times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective.     

Nasal peak inspiratory flow through Turbuhaler® in children with symptomatic rhinitis and in healthy children

Topical treatment of allergic or vasomotor rhinitis is possible by means of pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In children, little is known about nasal drug delivery by dry powder inhalation. The airflow through the device is critical for the drug release and a sufficient nasal inspiratory flow is needed for intranasal drug delivery from a dry powder inhaler. In order to investigate from what age children with allergic or vasomotor rhinitis can reliably use such a device, device-dependent nasal peak inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children aged 4–13 years making use of a dry powder inhaler (Turbuhaler^®) connected to a spirometer (Vitalograph^®). In the clinically relevant context, instructions from the doctor and one week's use of a Turbuhaler at home were found to be sufficient to obtain a good inhalation technique and were shown to improve DnPIF at least as effectively as visual feedback training at the clinic. Children with rhinitis, as well as healthy children from the age of 6 years, were able to generate a DnPIF sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF values correlated with age. Consequently, a recommendation to use a nasal Turbuhaler from the age of 6 for topical drug delivery in the treatment of allergic or vasomotor rhinitis seems reasonable.     

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case–control study on 171 patients. The EFESO-children Multicenter Trial

Sublingual‐specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in ‘real life’ in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case–control study to evaluate the effect of SLIT in children (age 6–18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case–control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone^® ALK‐Abellò). Controls (n = 81) were defined as sex‐age‐ and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean ± SD) was 4.5 ± 2.5 in cases and 9.0 ± 3.0 in controls (?50%) (p = 0.0001). MS (mean ± SD) was 2.5 ± 1.9 and 3.6 ± 2.1 in the case and control groups, respectively (?31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2‐yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.