Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Increased sensitivity to staphylococcal enterotoxin B following adenoviral infection

Staphylococcal enterotoxin B induces toxic shock and is a major virulence factor of staphylococcal diseases. We examined the effects of systemic adenoviral infection on responses to staphylococcal enterotoxin B in a murine model. We found that adenoviral infection markedly increases the severity of liver injury following exposure to staphylococcal enterotoxin B without d-galactosamine sensitization. In adenovirus-infected mice, staphylococcal enterotoxin B triggered a more profound hypothermia and increased apoptosis in the liver. Consistent with these observations, we also found that adenoviral infection primed for an increased production of gamma interferon in vivo and in vitro following stimulation with staphylococcal enterotoxin B. Gamma-interferon-knockout mice did not show increased sensitivity to staphylococcal enterotoxin B following adenoviral infection. These data suggest that a preexisting viral infection primes mice for subsequent staphylococcal enterotoxin B exposure, possibly via a gamma-interferon-mediated mechanism.     

Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and asthma

Although H1 antihistamine compounds (H1) are highly effective in the treatment of allergic rhinitis (AR), their role in the treatment of asthma is still controversial. Because a strong association between AR and bronchial hyperresponsiveness (BHR) has been reported, this study was designed to assess the effect of a new H1 anti histamine, cetirizine (C), on nonspecific BHR in patients with AR. Twelve patients were included in a double-blind, crossover, placebo-controlled trial. All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge. After a washout period of 1 week to ensure the stability of the BHR, the patients received, by crossover randomization, C 10 mg daily or placebo (P) for 2 weeks. After each treatment period, BHR and nasal blocking index (NBI) were measured 1 and 6 h after nasal challenge. Bronchial responsiveness was expressed as methacholine PD20, the provocation dose of methacholine causing a 20% decrease in FEV1. Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 (median) measured before challenge showed no difference after cetirizine or after placebo (1.36 mg). Results 1 h after allergen did not show significant differences between C (methacholine PD20=0.522 mg) and placebo (methacholine PD20=0.455 mg). By contrast, 6 h after challenge, methacholine PD20 was 0.918 mg for C and 0.483 mg for P (P=0.042). Similarly, NBI showed no change between C and P 1 h after challenge, whereas the difference was significant 6 h after challenge (P=0.011 ). These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR. They suggest that C may be useful in patients with asthma associated with AR.     

Bacterial allergy in allergic rhinitis and bronchial asthma.

Nineteen patients suffering from allergic rhinitis and bronchial asthma were studied for bacterial allergy with Staphylococcus aureus, Kelbsiella pneumoniae and Diplococcus pneumoniae. Allergy skin tests, provocative tests and the Migratory Inhibition Factor were employed. The correlation indicates to the authors that bacterial allergy is more important than bacterial "infection" as a cause of allergic rhinitis and asthma in many instances. This is often overlooked by practicing allergists.     

The comparison of allergic responses to Dermatophagoides farinae between bronchial asthma and allergic rhinitis

The allergic responses of 52 bronchial asthma patients who exhibited a positive bronchoprovocation test with house dust and 50 allergic rhinitis patients who had positive RAST results to Dermatophagoides farinae (D. farinae) were studied, including the measurement of D. farinae-specific IgE using D. farinae-RAST, total IgE and skin reactivity to D. farinae and house dust. A comparison between the allergic rhinitis group in which methacholine PC20 was more than 4.66 mg/mL and the allergic rhinitis group which presented negative results in the methacholine bronchial challenge test, indicated that there were significant differences in skin test reactivity and the ratio of specific IgE to total IgE (P less than .05). The allergic responses we observed were not different between the allergic rhinitis group in which methacholine PC20 was less than 4.66 mg/mL (asthmatic range of methacholine PC20) and the allergic rhinitis group in which methacholine PC20 was more than 4.66 mg/mL. When comparing the bronchial asthma group which showed positive results in D. farinae-RAST and the allergic rhinitis group in which methacholine PC20 was less than 4.66 mg/mL, significant differences were noted in total IgE level (P less than .05). These findings suggest that the development of bronchial asthma in patients with allergic rhinitis might be predicted by measuring the degree of bronchial hyperreactivity and their allergic responses.     

Deficient Concanavalin-A-induced suppressor-cell activity in patients with bronchial asthma, allergic rhinitis and atopic dermatitis

Concanavalin-A (Con-A)-induced suppressor activity against the proliferative response of autologous lymphocytes to phytohaemagglutinin (PHA) was examined in the peripheral-blood lymphocytes from fourteen patients with bronchial asthma, ten patients with allergic rhinitis and eleven patients with atopic dermatitis and compared with eleven simultaneously studied healthy normals. Eight of fourteen patients (57%) with bronchial asthma, eight of ten patients (80%) with allergic rhinitis and five of eleven patients (45%) with atopic dermatitis demonstrated deficient Con-A-induced suppressor function. Abnormal suppressor-cell functions could play an important role in the pathogenesis of atopic states.     

Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D.

Mice (BALB/cJ, C3H/HeN, and C3H/HeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C3H/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an important cofactor in intoxication. In a time course study of the illness, prominent pathological changes characterized by blood congestion and thickening of alveolar septa were seen in the lung, while blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen, congestion, inflammation, and lymphoid cell depletion were the major reactions. The pathological features of the mice had many similarities to those of rhesus monkeys intoxicated with intravenous SEB. The actinomycin D-primed C3H/HeJ mice are thus an ideal mouse model for studying SEB toxicosis and toxic shock.     

Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P = 0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: 1) In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. 2) MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms. 3) It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.     

The levels of CD4+CD25+ regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma

Our purpose was to determine whether numbers of CD4(+)CD25(+) T [T regulatory (T(reg))] cells and mRNA expression of functional molecules of T(reg) are related to airway allergy and disease severity in 51 paediatric patients with allergic rhinitis or bronchial asthma and 47 healthy controls. Surface markers were evaluated with flow cytometry, and mRNA was determined with real-time polymerase chain reaction. Children with allergic disease had fewer CD4(+)CD25(+) T cells (8 x 49% +/- 2 x 41% versus 9 x 58% +/- 2 x 43%, P<0 x 05) and CD4(+)CD25(hi) T cells (1 x 32% +/- 0 x 68% versus 1 x 70% +/- 0 x 68%, P<0 x 01) than control subjects. Numbers of CD4(+)CD25(+) and CD4(+)CD25(hi) T lymphocytes were higher in children with persistent allergic rhinitis and/or moderate-severe bronchial asthma than in those with respective milder disease. The number of T(reg) cells was correlated positively with total immunoglobulin E level. The mRNA expression of forkhead box P3 (FoxP3) was increased in moderate-severe versus mild asthma (2 x 93 +/- 0 x 38 versus 1 x 60 +/- 0 x 31, P< 0 x 01). Patients with moderate-severe bronchial asthma also had increased mRNA expression of interleukin (IL)-10 compared with patients with mild asthma (15 x 24 +/- 4 x 07 versus 3 x 77 +/- 2 x 18, P<0 x 01). The suppressive function of T(reg) cells from patients with more severe asthma was competent in vitro. On average, decreased numbers of T(reg) cells in children with allergic airway disease might represent a defect of the T(reg) population. With increased expression of FoxP3 and IL-10 in T(reg) from patients with relatively severe allergic disease, adaptive and functional T(reg) might be generated in response to aggravated atopy and disease severity.     

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.     

金黄色葡萄球菌肠毒素B在变态反应性疾病发病机制中的作用

变态反应性疾病的发病率逐年上升,Ⅰ型超敏反应是其主要的发病机制。近年来研究发现,金黄色葡萄球菌肠毒素B不但可以作为变应原诱导变态反应性疾病的发生,而且还可以作为超抗原影响免疫调节细胞和促炎细胞活性,在变态反应性疾病中发挥极其重要的作用。本文对金黄色葡萄球菌肠毒素B在变应性鼻炎、哮喘及特应性皮炎几种常见变态反应性疾病发生、发展中的作用机制作一综述。     

Systemic levels of ceruloplasmin oxidase activity in allergic asthma and allergic rhinitis

Context: The role of ceruloplasmin oxidase activity (COA) involving the interaction of oxidant and antioxidant balance in allergic diseases is still unknown.

Objective: Our study was designed to examine the changes in COAs in severe persistent asthma-allergic rhinitis, new diagnosed allergic asthma-allergic rhinitis and allergic rhinitis patients.

Methods: The study included 20 age- and sex-matched healthy individuals as control (Group I); Group II included 15 newly diagnosed allergic asthma-allergic rhinitis; Group III included 15 patients with severe persistent asthma-allergic rhinitis and in the fourth group there were 20 patients with allergic rhinitis. Group III was divided in two groups, severe persistent asthma-allergic rhinitis who were pre-(III-A) and post-treated (III-B) with omalizumab. Group IV was divided to two groups, pretreatment (IV-A) and posttreatment (IV-B) with specific subcutaneous immunotherapy modalities. All the posttreatment measurements were 12 months after the therapy. All the patients were assessed by the skin prick test, high sensitive C-reactive protein (hs-CRP) and COA.

Results: There were significant differences between Group I and Groups III-A, III-B, IV-A and IV-B; Group II and Groups III-A, III-B, IV-A and IV-B; Group III-A and Groups III-B, IV-A and IV-B; Group III-A and Groups IV-A and IV-B; and Group IV-A and IV-B. Interestingly, there was a correlation between the hs-CRP and COA levels in Group III-A.

Conclusions: Our data suggest that hs-CRP and COA levels might be an indicator of an inflammation and important in revelation of patients with allergy related diseases, especially of asthma patients.     

Prevalence and severity of allergic rhinitis in house dust mite-allergic patients with bronchial asthma or atopic dermatitis

BACKGROUND: Allergic rhinitis, asthma and atopic dermatitis are closely associated. Although population-based studies report a high prevalence of rhinitis among asthma patients, less is known of the association between rhinitis and atopic dermatitis and the severity of concomitant rhinitis. OBJECTIVES: We aimed to determine the prevalence and severity of allergic rhinitis among asthmatics and patients with atopic dermatitis and assessed whether age and comorbidity influence the severity of rhinitis signs and symptoms. METHODS: Three hundred and twenty-five patients recruited for a multicentre trial to study the effect of encasings of mattresses, pillows and duvets on signs and symptoms of allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue scores (VAS) and daily symptom scores and underwent nasal challenge tests with house dust mite (HDM). RESULTS: Based on history and clinical symptoms 92% of the 164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not result in a substantial lower prevalence of rhinitis. Subjects reported moderate symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of atopic dermatitis was associated with lower rhinitis VAS and symptoms scores, whereas in multivariate analysis the presence of asthma was positively associated with nasal responsiveness to HDM. CONCLUSION: The prevalence of nasal symptoms in patients with bronchial asthma or atopic dermatitis and sensitized to house dust mites is high. Although the majority of patients experience mild to moderate symptoms, the presence of nasal disease needs to be examined in all patients with atopic disorders.     

Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma.

Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.     

Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness

BACKGROUND: We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. OBJECTIVE: The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. METHODS: Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. RESULTS: Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6) pg/microg total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20) and 0.20 (0.12-0.35) ng/microg total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015 (0.011-0.021) compared with 0.010 (0.007-0.014) ng/microg total protein]. The level of ECP remained elevated off season. CONCLUSION: Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation.     

Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.     

Current immunological approaches for management of allergic rhinitis and bronchial asthma

A large population world over is affected with allergic diseases and asthma. Pharmacotherapy for allergic diseases and asthma is effective in controlling symptoms but on discontinuation of medication, symptoms reoccur. In contrast, immunotherapy modifies and corrects the underlying pathological immune responses in an antigen-specific manner. Immunotherapy shows an increase in IgG (blocking antibody) that competes with IgE for allergen, inhibiting the release of inflammatory mediators. Recent studies suggest that immunotherapy acts by modifying CD4+ T-cell responses either by immune deviation, T-cell anergy and/or both. Current immunological approaches for management of allergies and asthma involve immunization with native allergen, modified allergen, peptides/cDNA of allergen, anti-IgE, adjuvants coupled allergen, including immunostimulatory DNA sequences, cytokines, and bacterial products. These approaches modulate the immune response and are intended to give long-term benefit.     

Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma

BACKGROUND: Specific immunotherapy is the only potentially curative treatment in patients with allergic rhinitis and allergic asthma. Health economic evaluations on this treatment, particularly in a German context, are sparse. OBJECTIVE: To evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in addition to symptomatic treatment (ST) compared with ST alone in a German health care setting. METHODS: The analysis was performed as a health economic model calculation based on Markov models. In addition, we performed a concomitant expert board composed of allergy experts in pediatrics, dermatology, pneumology, and otolaryngology. The primary perspective of the study was societal. Additional sensitivity analyses were performed to prove our results for robustness. RESULTS: The SCIT and ST combination was associated with annual cost savings of Euro140 per patient. After 10 years of disease duration, SCIT and ST reach the breakeven point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787 per quality-adjusted life-year (QALY), with a range that depended on patient age (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a third-party payer's perspective, SCIT was associated with slightly additional costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients. CONCLUSIONS: Additional SCIT was associated with improved medical outcomes and cost savings compared with symptomatic treatment alone according to a societal perspective. Taking a European accepted ICER threshold of up to Euro50,000 per QALY into account, additional SCIT is considered clearly cost-effective compared with routine care in Germany. The degree of cost-effectiveness is strongly affected by costs related to SCIT and the target population receiving such treatment.