Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis

BACKGROUND: Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. OBJECTIVE: To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. METHODS: Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. RESULTS: All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. CONCLUSION: The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.     

Effect of pet removal on pet allergic asthma

BACKGROUND: Allergen avoidance has been recommended in the management of allergic asthma. Very few studies have assessed the effect of pet removal on pet allergic asthma. OBJECTIVE: We examined the effect of pet removal from homes on pulmonary function testing, airway hyperresponsiveness, and medication use. DESIGN: Prospective, nonrandomized, nonblinded observational study. PATIENTS AND METHODS: Subjects included 20 symptomatic patients with newly diagnosed pet allergic asthma who were keeping domestic animals, including hamsters, cats, dogs, and ferrets, and were sensitized to the animals. They were treated with inhaled corticosteroids or other medications according to recommendations by level of severity of the Global Initiative for Asthma. Methacholine inhalation tests were performed regularly before and after starting medication. Clinical features were compared between the patients who gave away their pets according to recommendations by the clinician (removal group) and the patients who refused to give away their pets (keeping group). RESULTS: There were 10 patients in both the removal group and the keeping group. After >or= 1 year of follow-up with or without pet removal, a 5.9-fold increase in the provocative concentration of methacholine causing a 20% fall in FEV(1) was observed in the removal group compared with a 2.3-fold increase in the keeping group (p = 0.04). There were no significant differences in the changes in FEV(1) and peak flow variability. Finally, no patient received inhaled corticosteroids in the removal group, whereas all but one of the patients needed beclomethasone dipropionate (mean dose, 600 mug/d) in the keeping group. CONCLUSION: This study indicates that removal of pets from homes reduces airway responsiveness in patients with pet allergic asthma more than optimal pharmacotherapy alone, thereby enabling a decrease in inhaled corticosteroid doses.     

Acute effects of 1-octen-3-ol, a microbial volatile organic compound (MVOC)--an experimental study

Acute effects were assessed from exposure to a common volatile compound of microbial origin, the aliphatic alcohol 1-octen 3-ol (octenol). Twenty-nine volunteers performed symptom reports, measurement of blink frequency by electromyography, measurement of the eye break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests and dynamic spirometry. Subjects were during 2h in random order exposed to either 10mg/m(3) of octenol or clean air as control. During octenol exposure subjective ratings of smell and nasal irritation were increased together with higher nasal lavage biomarker levels of eosinophil cationic protein, myeloperoxidase and lysozyme. Also eye irritation and blinking frequency were increased together with throat irritation, mild dyspnoea after 1-h but not after 2-h, and a small decrease in vital capacity. Ratings of headache and nausea were also increased. Atopics did not have more reactions due to exposure, whereas females experienced more smell and mucosal irritation. Thus, there were both subjective and objective signs of mild mucosal irritation of eyes and airways together with symptoms of headache and nausea.     

慢性荨麻疹患者的嗜酸性粒细胞阳离子蛋白和类胰蛋白酶测定

为研究嗜酸性粒细胞阳离子蛋白(ECP)、类胰蛋白酶(tryptase)在慢性荨麻疹中的变化,采用PHARMACIAUNICAP-100系统酶免疫荧光检测仪,分别对18例慢性荨麻疹患者和29名正常人作ECP和tryptase检测。结果,慢性荨麻疹患者组ECP测定值为7.74±9.35ng/L,阳性率为27.8%。正常对照组ECP测定值为2.33ng/L,阳性率为0。两组对比有明显差异(P<0.01)。慢性荨麻疹患者组tryptase测定值为7.34±5.02ng/L,阳性率为72.2%。正常对照组tryptase测定值为4.15±1.52ng/L,阳性率为10.34%。两组相比也有明显差异(P<0.01)。慢性荨麻疹患者中存在嗜酸粒细胞和肥大细胞的激活,其释放的ECP和tryptase可分别作为嗜酸性粒细胞和肥大细胞激活的标志物,并可能提示与I型变态反应的延缓相有关。     

复方氢溴酸右美沙芬联合头孢羟氨苄治疗小儿支气管炎的临床研究

目的 观察复方氢溴酸右美沙芬联合头孢羟氨苄治疗小儿支气管炎的临床效果。方法 选择2017年8月-2019年10月在洛阳市妇幼保健院治疗的小儿支气管炎患儿147例,随机分为对照组（74例）和治疗组（73例）。对照组口服头孢羟氨苄颗粒,每次15~20 mg/kg,2次/d;治疗组在对照组的基础上口服复方氢溴酸右美沙芬糖浆,2~3岁3 mL/次,4~6岁4 mL/次,6~9岁5 mL/次,3次/d。两组患儿均连续治疗7 d。观察两组患者临床疗效,同时比较治疗前后两组患者炎性因子半胱氨酰白三烯（CysLTs）、呼出气一氧化氮（FeNO）和嗜酸性细胞阳离子（ECP）水平,及临床症状消失时间。结果 治疗后,对照组临床有效率为78.38%,显著低于治疗组的94.52%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组CysLTs、FeNO和ECP水平均显著降低（P<0.05）,且治疗组明显低于对照组（P<0.05）。治疗后,治疗组临床症状消失时间明显比对照组短（P<0.05）。结论 复方氢溴酸右美沙芬联合头孢羟氨苄治疗小儿支气管炎,可快速改善患儿临床症状,缓解机体炎症反应,临床疗效较好。     

Feasibility of extracorporeal photopheresis in pediatric patients with graft‐versus‐host disease after hematopoietic stem cell transplantation

Graft‐versus‐host disease (GVHD) is a main cause of morbidity and mortality following hematopoietic stem cell transplantation. The cumulative incidence of acute and chronic GVHD (aGVHD, cGVHD) reaches 30%‐50% and 20% in pediatric populations, respectively. Prednisolone and/or calcineurin inhibitors (CNI) are first‐line treatments, but no superior second‐line treatment has yet been established. Several treatments have been suggested, among others extracorporeal photopheresis (ECP). Technical advances have made treatment of pediatric patients possible; however, only few reports on the feasibility of ECP in children have been published. We retrospectively studied the feasibility, safety, and efficacy of ECP in 15 children with steroid‐dependent/refractory acute or chronic GVHD, who initiated ECP treatment between April 2014 and January 2018. Only few and mild side effects directly related to the ECP procedure were registered, even in patients with low body weight. The most frequent cause of shortened or canceled ECP treatment was difficulties with vascular accesses, which were more rarely seen using central venous catheters with larger lumens and made of stiffer material. Nine patients had grade II‐III aGVHD. Six of these experienced a response to ECP at day 28, while eight of nine had responded at the last ECP treatment. Six patients had cGVHD when ECP was initiated, and of these, four had a partial response at last ECP treatment. We found ECP to be a feasible and safe treatment, and particularly, children with aGVHD appeared to respond well to ECP.     

Increasing the collection flow rate to 2 mL/min is effective and reduces the procedure time in off-line photopheresis

Background

Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T-cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off-line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat.

Study design and methods

In this prospective study, data of routinely performed off-line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2).

Results

A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 10⁹ respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%.

Conclusion

The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate.