Nasal histamine reactivity; relationships to skin-test responses, allergen provocation and symptom severity in patients with long-continuing allergic rhinitis

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.     

Nasal provocation tests with house dust mite in patients with perennial rhinitis

The aim of this study was to evaluate a response of the upper airways mucosae to allergens house dust mite: Dermatophagoides farinae and Dermatophagoides pteronyssinus. Compared were results of nasal challenge with results of skin prick tests. 87 patients with perennial rhinitis allergic to Dermatophagoides farinae and/or Dermatophagoides pteronyssinus were included. There were 58 men, 29 women, age 18-54 years, mean age 26 years. Nasal provocation tests were performed first with solvent, and next if flow rate did not change more than 20%, with Dermatophagoides farinae and Dermatophagoides pteronyssinus extracts. The nasal response was evaluated with active anterior rhinomanometry. Nasal flow was measured at 15, 30 and 45 minutes after allergen challenge. There were 99% positive skin prick tests Dermatophagoides farinae and 94% positive skin prick tests Dermatopagoides pteronyssinus. Nasal provocation tests with Dermatophagoides farinae extract were positive in 63% patients and Dermatophagoides pteronyssinus extract--in 62% patients. Majority of nasal challenges were positive at 15th minute. There is association between skin prick tests Dermatophagoides farinae and Dermatophagoide pteronyssinus 4+ and positive nasal provocation tests with the same allergen (p < 0.05). We have found correlation between skin tests Dermatophagoides farinae and Dermatophagoides pteronyssinus (correlation index = 0.58) and no correlation between nasal provocation Dermatophgoides farinae and Dermatophagoides pteronyssinus extracts. CONCLUSION: Nasal provocation tests are more specific than skin prick tests in patients with perennial rhinitis.     

Allergen-induced specific and non-specific nasal reactions. Reciprocal relationship and inhibition by topical glucocorticosteroids

The correlation between allergen-induced specific and non-specific (histamine) nasal reactions was studied, especially as regards topical glucocorticosteroid effects on the non-specific reactions. Thirteen patients with strictly seasonal allergic rhinitis participated. A nasal challenge with histamine and three increasing doses of allergen was performed on the first day. The patients were rechallenged 24 h later with the same histamine dose and the lowest allergen dose from the previous day. The same 2-day challenge was also performed after pretreatment for one week with budesonide in 8 of these patients. Symptom scores were recorded. The N-alpha-tosyl-L-arginine-methyl-esterase (TAME esterase) activity in nasal lavages was determined. The nasal symptoms and the TAME-esterase activity increased at rechallenge for both histamine and allergen, compared with the initial challenge. The mean ( +/- SE) composite nasal symptom score after histamine increased from 3.5 +/- 0.49 to 4.9 +/- 0.35 (p less than 0.01) and after allergen from 1.62 +/- 0.3 to 3.2 +/- 0.5 (p less than 0.01) at rechallenge. Similar increases were recorded for the TAME-esterase activity. A close correlation between the allergen-induced increase in specific (allergen) and non-specific (histamine) reactivity was found (r = 0.7, p less than 0.01, composite nasal symptom score). Treatment with topical glucocorticosteroids abolished the allergen-induced increase in both specific (p less than 0.001) and non-specific (histamine) (p less than 0.01) nasal reactivity.     

Nasal responsiveness to methacholine stimulation in allergic rhinitis patients

Summary We examined the nasal responsiveness to topical methacholine application in allergic rhinitis and non-allergic chronic rhinitis patients, and in control subjects. Methacholine responsiveness was significantly higher in allergic rhinitis patients than in non-allergic patients and control subjects. In perennial rhinitis, methacholine responsiveness correlated with the severity of daily nasal symptoms and those provoked by specific allergen challenge tests. Among nasal symptoms, hyper-rhinorrhoea was found to be closely related to methacholine responsiveness. As a result of these findings, the possibility of cholinergic hyper-reactivity in allergic rhinitis patients is discussed.     

Diagnosis of nasal allergy to the house dust mite

Twenty-five patients with perennial rhinitis and a positive skin prick test (SPT) for Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) were submitted to nasal provocation and the radioimmunosorbent test (RAST) for specific IgE-antibodies. We found a significant correlation in the reaction to both allergen extracts for all parameters examined. In addition, there was a significant correlation among the SPT, the RAST and the nasal provocation for Dp and between the SPT and the RAST for Df. In patients with perennial rhinitis we recommend the combination of all three methods to differentiate unspecific rhinitis from an allergic rhinitis. Only the patients with proved allergic rhinitis could benefit from a specific hyposensitisation.     

The effect of allergen provocation on the nasal cycle estimated by acoustic rhinometry

CONCLUSION: The overall duration and reciprocity of the nasal cycle were not changed after allergen provocation. The duration of immediate response was 38 min, but the amplitude of the nasal cycle was increased significantly after allergen provocation. OBJECTIVE: Nasal airflow is asymmetrical and subjected to spontaneous reciprocal changes which are referred to as the nasal cycle. Limited information is available on how this is affected by allergens. The purpose of this study was to evaluate the effects of allergen provocation on the nasal cycle. MATERIALS AND METHODS: This study was performed on 25 patients with allergic rhinitis and 25 subjects in a control group with no symptoms of allergic rhinitis. Acoustic rhinometry was used to test patients before and after allergen provocation. The patients underwent acoustic rhinometry at 15-min intervals for evaluation of nasal cycle and 3-min intervals for immediate response. RESULTS: With the allergic patients, 21 of the 25 patients (84.0%) showed a nasal cycle and they still had a nasal cycle after the allergen provocation. In the study on the changes in the immediate responses, the average recovery time was 38 min and the reduction rate of the non-patent side was higher than that of the patent side. Also, the average period of the nasal cycle was 153 min before the allergen provocation and 140 min on average after the allergen provocation; there were no statistical differences. The amplitude of each nasal cycle increased after allergen provocation and the difference had statistical meaning.     

A multicenter trial of specific local nasal immunotherapy

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.     

粉尘螨点刺试验与粉尘螨鼻黏膜激发实验相关性分析

目的评价目前粉尘螨过敏的常年性变应性鼻炎（AR）患者皮肤点刺试验（skin prick test,SPT）和鼻黏膜激发实验（nasal provocation test,NPT）的相关性。方法选择90例临床症状及体征符合常年性AR的患者行SPT及NPT。结果粉尘螨SPT及NPT灵敏度分别为84.6%和100%,其SPT及NPT的特异度分别为94.1%和98.0%。阳性级别在（＋＋）、（＋＋＋）和（＋＋＋＋）的SPT阳性患者,NPT阳性率分别为24.2%、30.3%和45.5%。结论 SPT为诊断AR的必要先行检查手段,NPT对于可疑变应原的确诊、鼻黏膜的非特异性高反应性的诊断及特异性免疫治疗（specific immunotherapy,SIT）具有较高价值。SPT级别强度越高,NPT阳性率越高,但SPT级别强度与NPT液浓度之间无明显相关性。     

Local and systemic immunotherapy in nasal allergy

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.     

The effect of allergen provocation on the nasal cycle estimated by acoustic rhinometry

Conclusion. The overall duration and reciprocity of the nasal cycle were not changed after allergen provocation. The duration of immediate response was 38 min, but the amplitude of the nasal cycle was increased significantly after allergen provocation.

Objective. Nasal airflow is asymmetrical and subjected to spontaneous reciprocal changes which are referred to as the nasal cycle. Limited information is available on how this is affected by allergens. The purpose of this study was to evaluate the effects of allergen provocation on the nasal cycle.

Materials and methods. This study was performed on 25 patients with allergic rhinitis and 25 subjects in a control group with no symptoms of allergic rhinitis. Acoustic rhinometry was used to test patients before and after allergen provocation. The patients underwent acoustic rhinometry at 15-min intervals for evaluation of nasal cycle and 3-min intervals for immediate response.

Results. With the allergic patients, 21 of the 25 patients (84.0%) showed a nasal cycle and they still had a nasal cycle after the allergen provocation. In the study on the changes in the immediate responses, the average recovery time was 38 min and the reduction rate of the non-patent side was higher than that of the patent side. Also, the average period of the nasal cycle was 153 min before the allergen provocation and 140 min on average after the allergen provocation; there were no statistical differences. The amplitude of each nasal cycle increased after allergen provocation and the difference had statistical meaning.     

天门地区变应性鼻炎吸入性变应原皮肤点刺试验结果分析

目的 了解天门地区变应性鼻炎患者的变应原种类、分布情况。方法 用11种变应原对天门地区变应性鼻炎疑诊患者行皮肤点刺试验,详细采集病史资料。结果 710例（87%）患者变应原呈阳性反应,阳性率相对较高的变应原依次为屋尘螨、粉尘螨、无爪热带螨、德国小蠊及狗毛皮屑,单一的变应原反应阳性者少,多数为2种或2种以上发生变应原阳性反应,其中大多数是螨类,男女差异无统计学意义,儿童组与成人组变应原阳性率有统计学意义。结论 天门地区变应性鼻炎的主要变应原为螨类,男女之间阳性率无明显差异,儿童阳性率高于成人。     

慢性鼻窦炎鼻息肉与变应性因素相关性的探讨

目的 探讨变应性因素在慢性鼻窦炎鼻息肉发病中的作用。方法回顾性分析1882例慢性鼻窦炎鼻息肉患者术前鼻腔分泌物涂片嗜酸粒细胞及变应原皮肤试验检查结果，并将其变应性症状和体征出现的比例与临床分型分期加以比较。结果①1882例慢性鼻窦炎鼻息肉患者中60．4％(1137例)的患者伴有不同程度的变应性症状和体征，25．3％(477例)的患者合并变应性鼻炎，2．1％(39例)的患者合并支气管哮喘；②在Ⅰ型(708例)和Ⅱ型(823例)各分期的患者中，合并变应性鼻炎及支气管哮喘的发生率和嗜酸粒细胞、皮肤变应原试验阳性率以及变应性鼻炎临床症状出现的百分率分别由低到高出现，Ⅱ型3期各项比例最高；③42．2％(795例)的患者变应原皮肤试验阳性，其中94．3％对常年性变应原呈阳性反应；④26．3％(495例)的患者伴有变应性鼻炎的临床症状，其中99．8％(494／495例)为常年性发作；⑤有前期手术史的病例占38．9％(732例)，其中合并变应性鼻炎者占有前期手术史例数的38．3％(280例)，占合并变应性鼻炎患者的58．7％(477例)。结论变应性因素特别是常年性变应性鼻炎与慢性鼻窦炎鼻息肉的病变程度和病变范围有关。同时变应性鼻炎也促进了疾病的复发。     

长沙地区562例变应性鼻炎患儿变应原谱分析

目的:调查长沙地区变应性鼻炎患儿的变应原分布情况及其阳性率,并分析其相关因素。方法:应用13种标准化吸入变应原对562例变应性鼻炎患儿进行变应原皮肤点刺试验,并详细采集病史资料。结果:457例呈阳性反应(81.3%),其主要变应原均为粉尘螨和屋尘螨,其次为热带螨、美洲大蠊、德国小蠊及狗毛等。花粉变应原在该组十分少见,城市儿童变应性鼻炎的患病率显著高于农村(P<0.01)。结论:长沙地区变应性鼻炎患儿的主要变应原为尘螨,与居住环境有关,多数患儿可应用螨变应原进行特异性免疫治疗。变应原皮肤点刺试验应用于儿童变应性鼻炎的诊断是一种安全的方法。     

Persistent allergic rhinitis includes different pathophysiologic types

BACKGROUND: Allergy rhinitis is typically classified as seasonal allergy rhinitis (SAR) and perennial allergy rhinitis (PAR). More recently, the Allergic Rhinitis and its Impact on Asthma document proposed the intermittent (ITR) and persistent forms (PER). However, it has been previously reported that each single allergen may induce different clinical and pathophysiologic features. OBJECTIVE: The aim of the study was to test the hypothesis that the type of causal allergen might characterize pathophysiologic differences in a cohort of patients with PER. METHODS: Three hundred nineteen patients, sailors of the Italian Navy, with moderate-severe PER were prospectively and consecutively evaluated with clinical evaluation, skin prick test, rhinomanometry, and nasal decongestion test. RESULTS: Patients with pollen allergy showed significantly more severe symptoms, lower nasal airflow, and higher response to decongestion test than patients with allergy to perennial allergens (P < .0001). CONCLUSION: This study provides evidence that patients with PER may show different pathophysiologic patterns depending on the type of causal allergen.     

长沙地区3 000例变应性鼻炎变应原皮试结果分析

摘要：目的了解长沙地区变应性鼻炎变应原皮试结果,为变应性鼻炎患者的预防及诊治提供参考。方法随机选择诊治的变应性鼻炎患者3 000例,采用标准测量方法用点刺原液进行变应原测试,分析其结果,并探讨阳性病例在性别方面的多项差异性。结果3 000例变应性鼻炎患者中,阳性者2 631例,阳性率87.70%。其中粉尘螨阳性者2 463例,阳性率82.10%;屋尘螨阳性者2 235例,阳性率74.50%;蟑螂阳性者1 250例,阳性率42%。其中粉尘螨（+）351例,（++++）932例;屋尘螨（+）250例,（++++）837例;蟑螂（+）1 003例,（++++）39例。其中女性患者1 500例,阳性1 269例,阳性率84.60%;300例单一阳性变应原中,蟑螂131例,尘螨120例。男性患者1 500例,阳性1362例,阳性率90.08%;300例单一阳性变应原中,蟑螂162例,尘螨126例。结论点刺原液检出9种变应原阳性结果主要是粉尘螨和屋尘螨,蟑螂与变应性鼻炎的关系仅次之;3种主要变应原中阳性强度最高的主要是粉尘螨和屋尘螨;女性患者阳性率较男性低,另单一阳性变应原中,女性对尘螨阳性率最高,男性对蟑螂阳性率最高。     

变应原点刺实验及其和鼻黏膜激发实验的相关性研究

目的:研究变应性鼻炎患者变应原的分布情况及其和鼻黏膜激发实验的相关性,以确定阳性变应原不同等级在诊断变应性鼻炎中的可靠性。方法:采用阿罗格公司生产的标准化变应原试剂,对有临床症状和体征的1400例患者进行了吸入性变应原的皮肤点刺实验,同时选择阳性变应原不同等级的各30例螨阳性的患者行鼻黏膜激发实验,以评价两者的相关性。结果:变应原阳性患者1 088例(78%),其中螨过敏890例(81.8%);单纯常年性变应原阳性率为52.2%(568例),单纯性季节性变应原为35.7%(388例),两者皆有者12.1%(132例)。阳性变应原等级为+++和++++患者鼻黏膜激发实验皆为阳性,等级为++的有1例为阴性,等级为+的患者中鼻黏膜激发实验有9例为阴性,而在变应原为阴性的患者中有5例为阳性。结论:变应原阳性等级较高的患者其鼻黏膜激发实验皆为阳性,而在较低等级阳性患者中有假阳性发生,在变应原实验为阴性患者中亦存在假阴性。因此临床上在挑选患者行免疫治疗前,应考虑上述情况。     

Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses after allergen and histamine provocation

We investigated nasal passage patency after allergen and histamine provocation in patients with allergic rhinitis by acoustic rhinometry. In total, 75 outpatients with allergic rhinitis were studied. The threshold of nasal hypersensitivity to histamine was measured by the 10 μl instillation of serial 10-fold dilution in the ipsilateral nasal cavity. Nasal provocation testing to specific antigen was applied to the anterior part of inferior turbinate in bilateral sides in sitting position. Measurement of nasal patency by acoustic rhinometry was repeated three times in each nasal cavity. The minimal cross-sectional area and total volume of nasal cavity were measured in an individual subject. The minimal cross-sectional area and total volume in the histamine challenged-side significantly decreased on the 10⁻², 10⁻¹, 10⁻⁰ of end point, and up to 30 min after challenge with the threshold dose, but not in the unchallenged side. This means acoustic reflection technique is sensitive at least 100-fold in comparison with classical method like findings by anterior rhinoscopy and symptom scores. Nasal passage patency after bilateral allergen provocation showed predominant in the unilateral side, suggesting the cross over-reflex effects.It was concluded that acoustic rhinometry is one of the highly quantitative and sensitive method which can observe the change of nasal congestion.     

Thresholds in nasal histamine challenge in patients with allergic rhinitis, patients with hyperreflectory rhinopathy, and healthy volunteers

BACKGROUND: Characteristic symptoms of hyperreflectory rhinopathy include recurrent sneezing, nasal obstruction, and nasal secretion without an allergic background. The diagnosis can only be made if all differential diagnoses have been excluded. So far no clinical test has been established to reliably diagnose hyperreactivity of the nasal mucosa. The present study aimed to investigate whether nasal provocation with histamine allows identification of patients with hyperreflectory rhinopathy. MATERIALS AND METHODS: One-sided nasal challenge with histamine was applied to 13 patients with allergic rhinitis, 13 patients with hyperreflectory rhinitis, and 12 healthy volunteers. Histamine concentrations used were 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL. Test results were quantified using a symptom score (positive at values above 3) and active anterior rhinomanometry (positive at a reduction of airflow of 40% or more in comparison to challenge with solvent). RESULTS: While there was a significant difference between controls and patients with allergic rhinitis or hyperreflectory rhinopathy, respectively, no significant difference was observed between the two groups of patients. Results indicated that one-sided nasal provocation with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. In terms of the differentiation between subjects with hyperreactivity of the nasal mucosa and healthy controls, the sensitivity of one-sided nasal histamine provocation with 1 mg/mL was found to be 100%; its specificity was 83% if it was evaluated by rhinomanometry and symptom score. CONCLUSION: The present results indicate that one-sided nasal challenge with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. However, the test does not differentiate between patients with allergic rhinitis and patients with hyperreflectory rhinitis.     

变应原气道激发在变应性鼻炎和哮喘研究中的作用研究进展

随着城市化进程，环境及生活方式的改变，我国变应性疾病发病率逐年升高。目前认为变应性鼻炎和哮喘的发病主要是在遗传基因、环境因素共同作用下导致，但具体发病机制复杂，尚未完全清楚。慢性气道炎症和气道高反应性是变应性鼻炎和哮喘的典型的病理生理特征。环境中变应原的暴露可诱发疾病症状发作，引起气道及全身炎症反应增加，并导致气道敏感性/反应性升高。人为给予变应性鼻炎或哮喘患者呼吸道变应原吸入刺激，可以模拟其变应原自然暴露所致疾病症状发作，研究其病理生理变化，尚可通过药物干预评估其对症状及炎症抑制程度评估药物治疗效果。同时变应性鼻炎和哮喘作为上下气道疾病，相互影响，通过一端变应原刺激研究气道另一端症状及炎症反应，探讨上下气道之间的联系。屋尘螨为我国,特别是南方地区最主要、最常见的变应原，与疾病关系密切。主要从屋尘螨变应原鼻激发和支气管激发方法学及其在鼻炎和哮喘的研究中的应用作一综述。     

Effects of cetirizine on substance P release in patients with perennial allergic rhinitis

To evaluate the effect of cetirizine hydrochloride on substance P release in allergic rhinitis, we performed a single-blind placebo-controlled study of 14 patients with perennial allergic rhinitis (7 treated with cetirizine and 7 with placebo). After an initial nasal allergen challenge with lavages, the subjects received treatment with placebo or cetirizine hydrochloride (10 mg by mouth daily) for 1 week, followed by the second nasal allergen challenge with lavages. The levels of albumin, histamine, and substance P in nasal lavages before and after allergen challenge were quantified by enzyme-linked immunosorbent assay. Pretreatment of subjects with cetirizine reduced the level of substance P induced by antigen challenge, but did not significantly reduce levels of histamine. These results suggest that cetirizine may reduce nasal neurogenic inflammation by modulating the release of substance P in allergic rhinitis.