Peripheral Blood Neutrophil Activity During Dermatophagoides pteronyssinus-Induced Late-Phase Airway Inflammation in Patients with Allergic Rhinitis and Asthma

Recent investigations suggest that neutrophils may play an important role in the late-phase allergen-induced inflammation in allergic airway diseases. The aim of this study was to evaluate neutrophil chemotaxis, phagocytic activity, and reactive oxygen species (ROS) production in patients with allergic rhinitis and asthma challenged with inhaled Dermatophagoides pteronyssinus. Eighteen patients with allergic rhinitis and 14 with allergic asthma, all sensitized to D. pteronyssinus, as well as 15 healthy individuals underwent bronchial challenge with D. pteronyssinus. Peripheral blood collection and neutrophil isolation were performed 24 h before as well as 7 and 24 h after bronchial challenge. Neutrophils chemotaxis, phagocytic activity, and ROS production were analyzed by flow cytometer. Neutrophil chemotaxis and ROS production were increased, while phagocytic activity was decreased 24 h before challenge in patient groups compared with healthy individuals. After challenge, neutrophil chemotaxis and phagocytic activity increased after 7 and 24 h, when ROS production, only after 24 h. Bronchial allergen challenge had no influence for neutrophils activity in healthy subjects. Activated chemotaxis, phagocytic activity, and ROS production of peripheral blood neutrophils after challenge with D. pteronyssinus reflect an enhanced systemic inflammation in allergic rhinitis and asthma patients with induced late-phase airway inflammation.     

Asthma and Allergic Rhinitis in the Same Patients

This study from Danish general practice gives Figures about the simultaneous prevalence of asthma and allergic rhinitis and the order of onset among 7662 patients, who during 1 year consulted for one or both of these diseases. Twenty-eight percent of patients with asthma consulted because they also had allergic rhinitis, and 17% of patients with allergic rhinitis consulted because they also had asthma. Age- and sex-distributions are presented. In 25% of patients with both diseases the onset of both diseases occurred within the same year, while in 35% the onset of asthma occurred first and in 40% allergic rhinitis.
Among patients with both diseases, who did not have onset of both within the same year, more than 75% of them had onset of one disease within 2 years of the other.     

Serum Leptin Levels Depend on Allergen Exposure in Patients with Seasonal Allergic Rhinitis

Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. There are conflicting data about the role for leptin in allergic rhinitis. Therefore, the aim of the study was to evaluate the serum leptin levels in patients with seasonal allergic rhinitis (SAR), enrolled during and outside the pollen season, and in a group of healthy controls. The study included 137 subjects; 62 symptomatic SAR patients evaluated in season, 41 symptomless SAR patients out season, and 34 normal subjects. All subjects were consecutively evaluated. A skin prick test and blood sampling for assessing serum leptin levels were performed in all subjects. After analysing genders separately, symptomatic male patients had significantly higher levels than symptomless and normal subjects (p = 0.0004 and 0.0031 respectively), symptomatic female patients showed significantly higher levels than normal females (p = 0.0002). This study provides the evidence that leptin serum levels depend on allergen exposure in SAR patients.     

过敏性鼻炎患者总IgE、嗜酸性粒细胞和特异性IgE结果分析

目的 探讨血清总IgE(immunoglobulin E,IgE)水平及外周血嗜酸性粒细胞(eosinophil,EOS)计数在过敏性鼻炎(allergic rhinitis,AR)诊断中的作用,以及两者与血清特异性IgE(specific immunoglobulin E,sIgE)水平之间的关系。方法选择对蒿属花粉过敏的过敏性鼻炎患者60例作为鼻炎组,60例健康人作为对照组。将鼻炎组分为男性组与女性组,青年组(18~40岁)与中年组(41~65岁),将鼻炎组患者根据sIgE结果分为:中低水平(0.35 IU/mL≤sIgE<3.5IU/mL)、高水平(3.5 IU/mL≤sIgE<17.5 IU/mL)与极高水平(sIgE≥17.5 IU/mL)。结果 鼻炎组总IgE水平和EOS计数均高于对照组,差异有统计学意义( P <0.05);鼻炎组、男性组、女性组、青年组和中年组总IgE与sIgE均成正相关( r s =0.541,0.490,0.599,0.566,0.462,均 P <0.05);鼻炎组患者总IgE与sIgE等级成正相关( rs =0.449, P <0.05)。结论 血清总IgE可作为AR诊断辅助指标,联合检测血清总IgE及sIgE可为AR的诊断提供更充分的依据。     

Serum-Soluble HLA-G Is Associated with Specific IgE in Patients with Allergic Rhinitis and Asthma

Allergic rhinitis (AR) and allergic asthma (AA) are characterized by T helper (Th)2-polarized immune response. Soluble human leukocyte antigen G (sHLA-G) molecule plays an immunomodulatory activity. Previously, it has been reported that children with AR or AA had higher sHLA-G levels in comparison with normal subjects. Thus, the present study aimed at confirming these data in adults and investigating whether there was a relationship between serum sHLA-G levels and serum IgE levels, in patients with AR or AA. One hundred twenty symptomatic patients, suffering from respiratory symptoms, were enrolled: 45 non-allergic and 75 allergic. A group of 44 healthy subjects was considered as control. Serum sHLA-G levels and serum allergen-specific IgE were determined by immunoenzymatic methods. Allergic patients had significantly higher levels of sHLA-G molecules than non-allergic patients and normal controls (p?IgE both in AR (r?=?0.468) and AA patients (r?=?0.479). The present study confirms that serum sHLA-G molecules are significantly increased in allergic disease and demonstrates that sHLA-G levels are related with allergen-specific IgE levels.     

Seasonal Variation of Asthma and Allergic Rhinitis

The seasonal variation of consultations on account of asthma and allergic rhinitis, and the relationship with air concentrations of pollen, spores, and lead, cadmium, dust, soot and sulfur dioxide was investigated in Danish general practice during a 1-year period 1977-78. A population of about 500,000 was studied. Among about 3000 asthmatics there were less consultations during spring than the rest of the year, but the seasonal variation of consultations with symptoms was rather small. The highest rate of consultations was in week 24, which is close to the peak of the grass pollen period. No relationship was found between asthma symptoms and concentrations of pollution indicators. Among about 5000 patients with allergic rhinitis the rate of consultations with symptoms increased at the start of the tree pollen season, still more at the start of the birch pollen season, and was very high during weeks 21-26 in the grass pollen season. Two thirds of all consultations for symptomatic allergic rhinitis took place within 10 weeks (Nos. 18-27). During the grass pollen season there was a relative preponderance of young patients, while during the birch pollen season older patients dominated. No connection was seen between rhinitis symptoms and pollution indicators. The different seasonal variation of asthma and allergic rhinitis indicates that the two patient categories differ as regards symptom-provoking factors. Allergic rhinitis is mainly precipitated by grass and birch pollen. The precipitating factors of asthma were not disclosed in this study, with the exception perhaps of some influence from pollen, and - among 0-4-year-old children - respiratory infections.     

组胺激发试验对应变性鼻炎鼻粘膜微血管的影响

目的 研究组胺对应变性鼻患者鼻粘膜微血管的影响。方法 变应性鼻炎组28例,健康人组21例,用人体鼻粘膜微循环显微镜观察两组胺激发试验前后鼻粘膜微血管的管径、形态和管襻数的变化。结果 应变性鼻炎组组胺激发式试验后鼻粘膜微血管管径较激发前增粗,管襻数增加,鼻粘膜微血管形态以灯丝状以混合状增多。健康人组组胺激发试验前后鼻粘膜微血管管径、管襻数以形态均无变化。结论 变应性鼻粘膜微血管对组胺的反应性进行较健康人高,组胺对变应性鼻炎患者鼻粘膜容量血管和阻力血管均有舒张作用。     

Lymphocyte Subpopulations in Patients with Allergic Rhinitis

The lymphocyte subpopulations were classified using monoclonal antibodies specific for B lymphocytes (B1 antibodies), T lymphocytes (T11 and OKT3 antibodies), helper/inducer T cells (T4 antibodies) and suppressor/cytotoxic T cells (T8 antibodies). Three groups of subjects were studied: 20 normal controls, 29 patients with allergic rhinitis and a subgroup of nine patients who had received immunotherapy. The proportion of B lymphocytes, total T cells and T4 positive (helper/inducer) cells were not significantly different between the groups, but allergic patients were found to have a decreased proportion of suppressor T8 positive (suppressor/cytotoxic) cells and hence a high helper/suppressor cell ratio. These abnormal parameters were found to be normal in the group of allergic patients who had received immunotherapy. These results imply that a suppressor cell deficiency may be an underlying mechanism of allergic disease, and that immunotherapy could correct the suppressor cell deficiency.     

支气管哮喘与过敏性鼻炎患者对蟑螂变应原特异性IgE反应的对比研究

为比较支气管哮喘与过敏性鼻炎患者对不同种属蟑螂的过敏反应程度,探讨不同种属蟑螂间可能存在的交叉抗原性及其程度,用ELISA法检测支气管哮喘与过敏性鼻炎患者血清中对三种蟑螂(美洲大蠊、黑胸大蠊和德国小蠊)变应原的特异性IgE抗体(sIgE).结果显示支气管哮喘患者对美洲大蠊、黑胸大蠊和德国小蠊变应原的sIgE阳性率分别为23.5%、16.0%和14.0%,美洲大蠊sIgE阳性率比对德国小蠊为高,有显著性差异(P=0.015),虽然美洲大蠊sIgE阳性率比对黑胸大蠊高、黑胸大蠊sIgE阳性率比对德国小蠊高,但差异均无统计学意义(P=0.060;P=0.575);哮喘患者中美洲大蠊与黑胸大蠊sIgE反应符合率74.0%,美洲大蠊与德国小蠊sIgE反应符合率73.5%,黑胸大蠊与德国小蠊sIgE反应符合率85.0%.过敏性鼻炎患者对美洲大蠊、黑胸大蠊和德国小蠊sIgE阳性率分别为24.8%、17.6%和15.8%,美洲大蠊sIgE阳性率比对德国小蠊高,有显著性差异(P=0.040),虽然美洲大蠊sIgE阳性率比对黑胸大蠊高、黑胸大蠊sIgE阳性率比对德国小蠊高,但差异均无统计学意义(P=0.106,P=0.658);过敏性鼻炎患者对中美洲大蠊与黑胸大蠊sIgE反应符合率为73.9%,对美洲大蠊与德国小蠊sIgE反应符合率为75.2%,对黑胸大蠊与德国小蠊sIgE反应符合率为86.1%.过敏性鼻炎患者对美洲大蠊、黑胸大蠊和德国小蠊sIgE阳性率均比支气管哮喘患者高,但差异均无统计学意义(P=0.764;P=0.688;P=0.638).提示支气管哮喘与过敏性鼻炎患者对三种蟑螂的过敏反应程度基本相当,三种蟑螂间可能存在一定程度的交叉抗原性成分.     

The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients

Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L, 0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation.     

Levels, Complement Activity and Polymorphisms of Mannan-Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis

Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan-binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL-induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age-matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL-induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease ( P =  0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with 'A' allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that 'A' allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation.     

Long-term Effects of Specific Allergen Immunotherapy Against House Dust Mites in Polysensitized Patients With Allergic Rhinitis

Purpose

Allergen-specific immunotherapy is the only currently available treatment to modify the natural history of allergic rhinitis (AR). If patients are polysensitized, it is difficult to identify the allergen causing the allergic symptoms. We evaluated the effectiveness of immunotherapy against house dust mites (HDMs) in AR patients polysensitized to both HDMs and seasonal allergens.

Methods

Thirty AR patients polysensitized to both HDMs and seasonal allergens (group A) and 30 patients sensitized to HDMs only (group B) were enrolled in this study. All subjects who received immunotherapy against HDMs for more than 2 years were evaluated by the multiple allergen simultaneous test (MAST) to determine the specific IgE level in luminescence units, total eosinophil counts in peripheral blood, serum total IgE, total nasal symptom scores, and the rhinoconjunctivitis quality of life questionnaire (RQLQ) before and after immunotherapy.

Results

There were no statistical differences in levels of total and specific IgE, or total eosinophil count between the two groups. The total nasal symptom scores, RQLQ and medication scores significantly decreased after immunotherapy in both groups, however no significant differences were noted between the two groups.

Conclusions

We determined that the primary causative allergen of AR in Seoul, Korea is perennial allergens, such as HDMs, rather than seasonal allergens. This study provides a reference for the selection of allergens to use in immunotherapy for polysensitized AR patients living in an urban environment.     

Variations of Cationic Proteins from Eosinophil Leukocytes in Food Intolerance and Allergic Rhinitis

Challenge tests were performed in patients with food intolerance and allergic rhinitis to evaluate the usefulness of measurement of the eosinophil cationic protein (ECP) of serum to distinguish different allergic reactions. In one group of patients with food intolerance symptom-induced challenge resulted in a marked decrease of serum-ECP. The number of blood eosinophils decreased simultaneously in some but not all of these patients. In another group of patients with food intolerance serum-ECP displayed peak-like increases followed by a decrease. The decrease in serum-ECP may reflect that consumption of ECP is a result of idiosyncrasy in the target organ. In allergic rhinitis some patients showed an initial peak-like increase of serum-ECP, which was abolished by pretreatment with disodium-cromoglycate but not by pretreatment with antihistamine. Similar results have previously been demonstrated for allergic asthma. The difference obtained in serum-ECP upon challenge in typical reagin-mediated allergy and food intolerance may indicate that the latter is not reagin-mediated. However, the interpretation of data is difficult because of lack of knowledge regarding the turnover in the circulation of ECP.     

Increased cys-Leukotrienes in Exhaled Breath Condensate and Decrease of PNIF after Intranasal Allergen Challenge Support the Recognition of Allergic Rhinitis in Children

Exhaled breath condensate (EBC) contains various mediators of inflammation. Since their concentrations correlate with severity of inflammatory response, EBC assessment allows non-invasive detection of various respiratory tract diseases and enables monitoring of their progression or treatment effectiveness. In this study, authors evaluate the usefulness of cysteinyl leukotrienes (cysLT) measurement in EBC, as non-invasive diagnostic markers of allergic rhinitis in children. It has been found that the assessment of cysLT in EBC, when performed out of the natural allergen exposure, can discriminate between healthy and allergic rhinitis individuals, with sensitivity 87.8 % and specificity 76.4 %, at the threshold level 39.05 pg/ml. The change of peak nasal inspiratory flow (ΔPNIF), measured before and after intranasal allergen challenge allowed recognition of healthy/allergic rhinitis-suffering individuals with sensitivity 76.8 % and specificity 78.6 %, at the threshold level of ?3.2 l/min. When ΔPNIF assessment was combined with the measurement of cysLT in EBC, the sensitivity of such diagnostic approach reached 100 % and its specificity increased up to 84.6 %. The proposed algorithm was found to sufficiently discriminate between allergic rhinitis-suffering and healthy children, however, its clinical usefulness especially in young children requires further studies.     

The Role of Anti-IgE Therapy in Combination with Allergen Specific Immunotherapy for Seasonal Allergic Rhinitis

Novel therapies that interfere specifically with immunologic mechanisms underlying allergen-induced pathology are currently in clinical evaluation. Among these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting the central mechanism of immediate-type hypersensitivity reactions. Application of anti-IgE antibodies effectively reduces IgE serum levels regardless of allergen specificity. Anti-IgE therapy has been successfully tested in patients with allergic rhinitis, asthma, and food allergy, showing significant efficacy in reducing symptom scores and the use of rescue medications. However, such therapy is limited by high costs and the requirements for permanent or every-season treatment. The advantage of specific immunotherapy (SIT) is the potential to alter the course of the disease, which has been demonstrated in patients with allergic rhinitis, insect venom allergy and, to a lesser degree, asthma. The broader application of SIT is restricted by sometimes life-threatening adverse effects. The combination of anti-IgE with SIT was suggested to be superior to each single treatment protocol in children and adolescents with allergic rhinitis. In a randomized, double-blind trial to assess the efficacy and safety of anti-IgE (omalizumab) or placebo in combination with SIT (birch pollen or grass pollen), the combination therapy reduced symptom load, the sum of daily symptom severity score plus rescue medication use, over the birch and grass pollen seasons by nearly 50% over SIT alone. These data show that the combination of anti-IgE plus SIT may be beneficial for the treatment of allergic diseases, offering improved efficacy, limited adverse effects, and potential immune-modifying effects.     

Specific Immunotherapy Normalizes Tryptophan Concentrations in Patients with Allergic Rhinitis

Background/Aims: An immune shift towards Th2-type immunity seems to be critical in the pathogenesis of allergic asthma and rhinitis. In a previous study, we found higher serum tryptophan concentrations in patients with seasonal tree or grass pollen rhinoconjunctivitis who underwent specific immunotherapy (SCIT) than in controls, and those with the highest levels at baseline responded less well to SCIT. In the present study, we examined whether 'booster immunotherapy' after cessation of SCIT had any influence on tryptophan metabolism during follow-up. Methods: Serum concentrations of tryptophan, kynurenine and neopterin were assayed in 19 patients (mean age: 26.2 years; 6 females) allergic to grass and/or tree pollen before and after they had received a booster immunotherapy with 4 injections of an allergoid vaccine (Pollinex Quattro; Bencard Vienna, Austria) over 8 ± 3 months outside the pollen season. Results: Serum tryptophan and kynurenine concentrations decreased after booster immunotherapy (mean ± SD, before immunotherapy: 81.1 ± 14.2 μmol/l, after immunotherapy: 61.4 ± 20.9 μmol/l and before immunotherapy: 2.25 ± 0.44, after immunotherapy: 1.69 ± 0.70 μmol/l, respectively; both p < 0.01); this was especially true in those responders who also tended to have lower baseline kynurenine concentrations as compared with nonresponders (p = 0.05). Finally, a correlation between changes in tryptophan metabolism and neopterin concentrations was observed after immunotherapy. Conclusions: The decrease in tryptophan and kynurenine concentrations following booster immunotherapy in hay fever patients strengthens the hypothesis that tryptophan metabolism might be involved in the course of allergic responses. However, it is still unclear whether the abnormal tryptophan metabolism in pollinosis patients is related to indoleamine 2,3-dioxygenase and/or to a specific cytokine background.     

变应性鼻炎大鼠动物模型的建立及评价

目的建立和评价SD大鼠变应性鼻炎模型。方法将SD大鼠随机分为对照组和模型组,模型组给予卵白蛋白(OVA)配合佐剂氢氧化铝全身致敏和局部致敏,建立SD大鼠变应性鼻炎模型;对照组以生理盐水代替OVA;HE染色检测鼻粘膜组织形态学变化;Wright’s染色检测模型组鼻腔分泌物和鼻粘膜组织嗜酸性粒细胞的表达;酶联免疫吸附测定法(ELISA)检测外周血IgE水平;通过行为学总积分对动物模型进行评价。结果模型组鼻粘膜组织纤毛脱落、倒伏,粘膜下腺体数量明显增加;模型组鼻腔分泌物中检测到大量嗜酸性粒细胞;模型组外周血IgE水平较对照组明显增高,具有统计学意义(P0.05);滴鼻后模型组喷嚏、抓鼻的次数及流涕等行为学总积分较对照组组明显增高,具有统计学意义(P0.05)。结论通过卵清蛋白配合佐剂氢氧化铝基础致敏和强化致敏,可成功建立SD大鼠变应性鼻炎动物模型,具有操作简单、重复性好、成功率高的优点,为今后变应性鼻炎的病变研究提供了有效的方法及组织形态学依据。     

哮喘诊断中甲襞微循环检测及过敏原皮试的相关性研究

同期对６４例过敏原皮试阳性的哮喘患者（以螨、蟑螂、屋尘、豕草、霉菌等阳性率较高）及５０例健康人甲襞微循环进行对比观察，发现患者组较健康组有明显的微循环障碍（Ｐ＜０．０１）。将哮喘患者的病情程度与其甲襞微循环、过敏原皮试的相关性作比较，结果表明：患者病情程度与其甲襞微循环改变相关非常显著（Ｐ＜０．０００１）；与过敏原皮试阳性程度有相关性（Ｐ＜０．０５）。