The common allergens in the Churg-Strauss syndrome

BACKGROUND: The asthmatic-prodromal phase of Churg-Strauss syndrome (CSS) is usually considered allergic, but data about the involved allergens are scarce. The aim of our work was to examine the prevalence of allergy in a group of CSS patients and in two control groups of persistent asthmatic subjects selected for eosinophilia >10% [first control group patients (CGP1)] and eosinophils <6% [second control group patients (CGP2)]. METHODS: The respiratory symptoms, and the results of prick test and/or RAST for the common allergens, performed before the vasculitic phase in 51 CSS, were retrospectively evaluated and compared with those of 46 CGP1 and 50 CGP2. RESULTS: 31.4% of CSS vs 67.4% of CGP1 (P = 0.0004) and vs 58.0% CGP2 (P = 0.007) were allergic. The number of subjects with seasonal allergies was lower in CSS vs CGP1 (P = 0.0069) and vs CGP2 (P = 0.0002). The number of perennial allergies was significantly higher in CSS than in both control groups (CSS vs CGP1, P = 0.0108; CSS vs CGP2, P = 0.0079). The subjects allergic to Dermatophagoides were prevalent in CSS vs CGP1 (P = 0.0045) but not vs CGP2. CONCLUSIONS: The evidence of allergy, considered as the demonstration of specific IgE consistent with the clinical history, is present in less than one-third of CSS and the higher prevalence of seasonal allergies in the controls disagrees with persistent asthma. Allergy may be only one of several mechanisms triggering exacerbation of asthma or supporting chronic airway inflammation as in asthma in general. Alternatively, unidentified allergens may play a role.     

AluyMICB dimorphism within the class I region of the major histocompatibility complex is associated with asthma and airflow obstruction in the Busselton population

AIM: To examine the association between the Alu dimorphism within the first intron of the MICB gene and asthma and airflow obstruction. Background The highly polymorphic non-classical MHC class I polypeptide-related (MIC) genes, MICA and MICB, encode stress inducible glycoproteins, which are expressed on a variety of epithelial cells, including those of the lungs. METHODS: AluyMICB genotyping was performed on 1109 subjects from the Busselton Health Study. From a standard questionnaire, 359 individuals indicated that they had been diagnosed by a doctor with asthma. Lung function was assessed by the forced expired volume in 1 second (FEV1) and expressed as a percent of the predicted value. Airflow obstruction was defined as FEV1<80% predicted. RESULTS: In men, a dominant relationship was found between the AluyMICB DD genotype and asthma (P=0.006; chi2(2)=7.65). Furthermore, multivariate analysis adjusted for age, height, weight and body mass index (BMI) showed a relationship between DD genotype and asthma in men in a dominant model (odds ratio (OR)=1.97; 95% confidence interval (CI)=1.11-3.51; P=0.021). In women, an association was found between the AluyMICB II genotype and FEV1 percent predicted as a continuous variable (P=0.001). When adjusted for age and BMI, it showed a significant relationship between AluyMICB and airflow obstruction in a dominant model (OR=14.11%, 95% CI 3.29-60.57, P<0.001). However, no association was found between the AluyMICB II genotypes and airflow obstruction in men. CONCLUSION: These findings suggest the possible involvement of a MHC class I gene in abnormal airway structure in women and airway function in men.     

Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation

BACKGROUND: In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. OBJECTIVE: To determine the degranulation status of circulating eosinophils in common allergic diseases. METHODS: Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. RESULTS: Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). CONCLUSION: In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.     

Evaluation of serum eosinophil cationic protein as a predictive marker for asthma exacerbation in patients with persistent disease

BACKGROUND: Eosinophilic inflammation is a feature of asthma. However, serological markers to indicate eosinophil activation in this process are not fully defined. OBJECTIVE: To evaluate the relationship of serum eosinophil cationic protein (ECP) to asthma worsening and a marker for treatment effectiveness, 26 adult patients with an asthma exacerbation were identified. METHODS: Identified asthma subjects were treated with oral corticosteroids (prednisone) for 14 days. The lung function variables, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), were determined as percentage of predicted and the blood total eosinophil count and serum ECP levels were measured. Patients were re-evaluated after 14 days of corticosteroid treatment and then every 3 months thereafter during a 12-month period. RESULTS: Eighteen patients responded to prednisone treatment, whereas eight did not, assessed as improvement of their lung function parameters. Different serum ECP patterns could be seen in the responders compared with the non-responders. All 18 responders had considerably increased serum ECP at the time of exacerbation, whereas the non-responders had lower serum ECP levels. The serum ECP levels decreased to a greater extent in the responder patient group than in the non-responder patients following prednisone treatment. This difference in patterns was not seen with total blood eosinophil counts. CONCLUSION: Our findings suggest that serum ECP may be used to predict a response to corticosteroid therapy in adult patients with asthma.     

Sputum basophils are increased in eosinophilic asthma compared with non‐eosinophilic asthma phenotypes

Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in “TH 2‐low” asthma phenotypes. Using flow cytometry, we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (P =0.007) with highest levels observed in eosinophilic asthma (EA ); median 0.22%, IQR 0.11%‐0.47%; n=14) compared with non‐EA (NEA) (0.06%, 0.00%‐0.20%; n=12; P <0.05). In asthmatics, basophils were positively correlated with sputum eosinophils (r =0.54; P <0.005) and inversely with sputum neutrophils (r =?0.46: P <0.05), but not with FEV ₁ (% predicted), FEV ₁/FVC or bronchodilator reversibility. In a subgroup initially identified as inadequately controlled asthma (n=7), there was a trend (P =0.08) towards a reduction in sputum basophils following increased inhaled corticosteroid (ICS ) treatment. Our findings suggest that basophils may be particularly important in eosinophilic asthma and that sputum basophil assessment could be a useful additional indicator of “TH 2‐high” asthma.     

Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction

BackgroundThe 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo.ObjectiveTo assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline.MethodsEnd points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb.ResultsOf 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils ≥ 150 cells/µL or FeNO ≥ 25 ppb and eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb, respectively. Similar results were observed in patient subgroups without PAO.ConclusionIn patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes.Trial Registration: ClinicalTrials.gov identifier: NCT02414854.     

Intranasal fluticasone propionate for chronic eosinophilic rhinitis in patients with aspirin-induced asthma

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32–60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with L-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects ( P =0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.     

支气管哮喘患者血清嗜酸细胞阳离子蛋白的变化

探讨检测血清嗜酸细胞阳离子蛋白在支气管哮喘的诊断１病情监测及疗效判断中的价值。方法采用荧光酶免疫法测定了发作期和缓解哮喘患者各２０例,慢性阻塞性肺疾病患者１６例和正常人２０例的血清ＥＣＰ,同时进行了肺功能测定,并对发作期哮喘患者在给予吸入皮质激素治疗３ｍｏ后复测其ＥＣＰ及肺。     

Evoked skin sympathetic potential in bronchial asthma patients with the hyperventilation syndrome

Patients with bronchial asthma hyperventilation syndrome are found to manifest an increase of the latent period of the evoked skin sympathetic potential as compared to patients without the hyperventilation syndrome. This attests to an autonomic neuropathy in the hyperventilation syndrome. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 286–287, March, 1994 Presented by A. D. Ado, Member of the Russian Academy of Medical Sciences     

Airway eosinophilic inflammation, epithelial damage, and bronchial hyperresponsiveness in patients with mild–moderate, stable asthma

Allergic asthma is characterized by chronic recruitment of eosinophils in the airways. Once activated, eosinophils release toxic products, including eosinophil cationic protein (ECP), able to damage airway epithelial cells. To test the hypothesis that also in mild-moderate stable asthma, a significant eosinophil activation could occur, we studied 25 asthmatic patients (34 ± 19 years old), of whom 18 were allergic (27 ± 12 years) and seven nonallergic (42±10 years), with FEV₁ values ±70% of predicted, and eight normal volunteers (controls, 33 ±11 years). All subjects underwent methacholine (MCh) challenge on the first visit, and bronchoalveolar lavage (BAL) on the second visit (approximately 3–4 days later). BAL cells were counted and albumin (Alb) (as index of protein dilution in BAL fluid) and ECP levels (as index of eosinophil activation) in BAL fluid were measured. As compared to controls, a significant increase in BAL eosinophil and in BAL epithelial cell numbers was observed in asthmatic patients (P>0.05, each comparison), with no differences between the two asthmatic patient subgroups. Detectable ECP levels (>2 μg/1) were found in BAL of 18 asthmatic patients (14 allergic and four nonallergic asthmatic patients), while Alb levels were measurable in 25 BAL fluids and found to be similar in controls and asthmatic patients, and in the two asthmatic patient subgroups (P>0.05, each comparison). In BAL of asthmatic patients, positive correlations were found between eosinophil numbers and 1) ECP/Alb levels (r= 0.50, P = 0.020); 2) epithelial cell numbers (r = 0.S0, P = 0.014). In asthmatic patients, a significant negative correlation was found between bronchial reactivity to MCh (log Pd₁₅) and ECP/Alb levels in BAL fluid (r=-0.6, P= 0.005), whereas no correlation was found between log Pd₁₅ MCh and BAL eosinophil or epithelial cell number (P>0.1, each correlation). These data suggest that bronchial eosinophil recruitment and activation may occur also in mild-moderate stable asthma and that bronchial epithelium damage and airway responsiveness may be partially associated with the eosinophilic inflammatory reaction.