Systemic ketoconazole is an effective treatment of atopic dermatitis with IgE-mediated hypersensitivity to yeasts

BACKGROUND: IgE-mediated hypersensitivity to yeasts is often seen in atopic dermatitis (AD) patients, especially when dermatitis is located in the head, neck, and shoulder regions. Two studies have shown the efficacy of ketoconazole in the treatment of this type of AD, in contrast to results of topical treatment. The objective was to assess the clinical efficacy of antifungal treatment in AD in a randomized, double-blind, placebo-controlled study with oral ketoconazole and yeast-specific IgE levels and saprophytic yeast growth monitored simultaneously. METHODS: Eighty patients with AD and positive P. ovale and/or C. albicans RAST/skin prick test results were randomized to receive ketoconazole or placebo for 30 days. The yeast growth of skin and pharynx; P. ovale, C. albicans, andS. cerevisiae RAST; serum total IgE; and the severity of the eczema (SCORAD) were assessed at day 0 and thereafter at 1 and 3 months. RESULTS: A significant improvement was seen in the SCORAD scale in the ketoconazole group at the second visit in comparison to the first visit (P<0.0005; n=36), but not in the placebo group (n=39). Of the individual determinants of the SCORAD, itching (P<0.005), the extent of dermatitis (area percentage), excoriation, lichenification (P<0.01), erythema, papulation, and dryness (P<0.05) improved significantly in the ketoconazole group. In the placebo group, only the extent of dermatitis (area percentage) decreased significantly (P<0.05). In the ketoconazole group, the number of positive P. ovale cultures decreased from 60% to 31% (n=35) compared to the placebo group (64% to 56%; n=39). The clinical response was most significant in female patients with positive yeast cultures. CONCLUSION: Saprophytic yeasts may be a source of allergens in AD. Thus, patients with AD, yeast growth, and elevated IgE levels to yeasts should be offered antifungal treatment.     

Anxiolytic premedication reduces preoperative anxiety and pain during oocyte retrieval. A randomized double-blinded placebo-controlled trial

BACKGROUND: The role of anxiolytic premedication remains unclear and significant postoperative side-effects may result from routine use. METHODS: In this double-blinded study, 100 infertile patients were randomized on the day of ultrasound-guided oocyte retrieval (TUGOR) by a computer-generated randomization list in sealed envelopes to receive either (i) 50 mg pethidine and 25 mg promethazine (premedication group) or (ii) normal saline (placebo group) i.m. 30 min prior to TUGOR. Anxiety level, pain levels and severity of postoperative side-effects were recorded. RESULTS: No differences were seen in demographic data, TUGOR duration, number of follicles punctured and clinical outcome. Preoperative anxiety level was significantly higher than the basal anxiety level in the placebo group only. The vaginal and abdominal pain levels during TUGOR and 4 h after TUGOR were significantly higher in the placebo group than the premedication group. Significantly more patients complained of drowsiness after TUGOR in the premedication group than the placebo group and other side-effects were comparable in both groups. CONCLUSION: Routine use of anxiolytic premedication prevented an increase of preoperative anxiety level, reduced pain levels during oocyte retrieval but was associated with a higher percentage of moderate/severe drowsiness in the postoperative period.     

Neostigmine for the treatment of acute colonic pseudo-obstruction.

BACKGROUND: Acute colonic pseudo-obstruction -- that is, massive dilation of the colon without mechanical obstruction -- may develop after surgery or severe illness. Although it may resolve with conservative therapy, colonoscopic decompression is sometimes needed to prevent ischemia and perforation of the bowel. Uncontrolled studies have suggested that neostigmine, may be an effective treatment. METHODS: We studied 21 patients with acute colonic pseudo-obstruction. All had abdominal distention and radiographic evidence of colonic dilation, with a cecal diameter of at least 10 cm, and had had no response to at least 24 hours of conservative treatment. We randomly assigned 11 to receive 2.0 mg of neostigmine intravenously and 10 to receive intravenous saline. A physician who was unaware of the patients' treatment assignments recorded clinical response (defined as prompt evacuation of flatus or stool and a reduction in abdominal distention), abdominal circumference, and measurements of the colon on radiographs. Patients who had no response to the initial injection were eligible to receive open-label neostigmine three hours later. RESULTS: Ten of the 11 patients who received neostigmine had prompt colonic decompression, as compared with none of the 10 patients who received placebo (P<0.001). The median time to response was 4 minutes (range, 3 to 30). Seven patients in the placebo group and the one patient in the neostigmine group without an initial response received open-label neostigmine; all had colonic decompression. Two patients who had an initial response to neostigmine required colonoscopic decompression for recurrence of colonic distention; one eventually underwent subtotal colectomy. Side effects of neostigmine included abdominal pain, excess salivation, and vomiting. Symptomatic bradycardia developed in two patients and was treated with atropine. CONCLUSIONS: In patients with acute colonic pseudo-obstruction who have not had a response to conservative therapy, treatment with neostigmine rapidly decompresses the colon.     

Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s, causing an intense systemic immune response and progressive lung damage. OBJECTIVE: We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA. METHODS: A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n = 29). Subjects received 400 mg of itraconazole per day (n = 15) or placebo (n = 14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatu s, and blood eosinophil counts. RESULTS: By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P <.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P <.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P <.01) and a decrease in IgG levels to A fumigatu s (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P =.03). There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group (P =.03). CONCLUSION: Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.     

Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization.

Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups.     

二甲双胍对奥氮平致精神分裂症肥胖患者肝脏脂肪含量的影响

目的:对奥氮平所致精神分裂症肥胖患者在接受二甲双胍治疗过程中,肝脏脂肪含量及血清内脏脂肪素的变化情况进行动态观察,并分析两者间的相互关系。方法:奥氮平治疗过程中出现肥胖的精神分裂症采用随机数字表法分为2组,分别接受二甲双胍(二甲双胍组,n=30)或安慰剂(安慰剂组,n=30)治疗,疗程12周。在治疗0周、12周时,分别测定肝脏脂肪含量、内脏脂肪素水平。结果:1治疗后12周时,二甲双胍组患者在肝脏脂肪含量显著下降(t=2.098,P0.05)的同时,内脏脂肪素也显著降低(t=2.832,P0.01);安慰剂组肝脏脂肪含量和内脏脂肪素的变化均不显著(P0.05);2二甲双胍组治疗前后肝脏脂肪含量、内脏脂肪素的下降值,均显著高于安慰剂组(t=6.204、3.403;P均0.001);3线性相关分析显示,二甲双胍组治疗前后肝脏脂肪含量的下降值与内脏脂肪素的下降值正相关(r=0.388,P0.05)。结论:二甲双胍可降低奥氮平致精神分裂症肥胖患者肝脏脂肪含量及内脏脂肪素水平,内脏脂肪素的下降可能参与了二甲双胍的降低患者肝脏脂肪含量的作用机制。     

Effects of allergen inhalation and oral glucocorticoid on serum soluble CTLA-4 in allergic asthmatics

BACKGROUND: The serum soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) concentration is significantly elevated in patients with asthma, and sCTLA-4 concentration correlate with the severity of asthma. The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum sCTLA-4 in patients with allergic asthma. METHODS: Allergen inhalation challenge was conducted in allergic asthmatics with isolated early asthma response and those with dual asthma response. In a randomized, double-blind, placebo-controlled, parallel group fashion, prednisolone or placebo was give orally once a day for 2 weeks. Venous blood samples were collected before and after allergen inhalation or prednisolone administration for obtaining sera. The serum sCTLA-4 concentrations were determined using enzyme-linked immunosorbent assay. RESULTS: The serum sCTLA-4 concentrations in the dual responder group increased from 29.0 (14.5-43.7) microg/l [median (25-75 percentiles)] before allergen inhalation to 44.0 (24.3-61.3) microg/l 24 h after allergen inhalation. In the isolated early responders, there were no significant increase in serum sCTLA-4 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum sCTLA-4 concentrations after 2 weeks of glucocorticoid therapy [22.0 (15.5-31.0) microg/l] compared with baseline values [37.0 (19.5-53.0) microg/l], whereas there was no significant difference in the placebo group. CONCLUSION: This study has demonstrated that serum sCTLA-4 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCTLA-4 concentrations were downregulated by prednisolone therapy.     

A randomized study of maintenance therapy with ranitidine to prevent the recurrence of duodenal ulcer

After an active duodenal ulcer has healed in response to medical therapy, the rate of recurrence during the subsequent year is relatively high. We therefore enrolled 140 patients with healed duodenal ulcers in a two-year randomized, double-blind trial comparing maintenance therapy (ranitidine, 150 mg nightly) with placebo for the prevention of recurrent duodenal ulceration. We performed endoscopy annually and when symptoms suggested the recurrence of ulcers. Verified recurrent ulcers in either group were treated for four or eight weeks with open-label ranitidine (150 mg twice a day). Patients whose ulcers healed within eight weeks resumed randomized treatment. Prophylactic therapy with ranitidine reduced the rate of ulcer relapses from 63 percent in the placebo group to 37 percent in the ranitidine group (P less than 0.05). Treatment with ranitidine extended the median ulcer-free interval from one to two years (P less than 0.05). The first recurrences of ulcer were asymptomatic in half the ranitidine group and in a quarter of the placebo group. Prophylactic therapy with ranitidine also reduced the frequency of recurrent ulcers that were unhealed by eight weeks, that were bleeding, that were in the stomach, or that were the second recurrent ulcer within six months, from 43 percent in the placebo group to 21 percent. Patients who drank alcohol, smoked, had a history of ulcer disease, or had duodenal scarring or erosion at the time of entry into the study were at the greatest risk for recurrence and benefited the most from prophylactic ranitidine. We conclude that prophylactic treatment with ranitidine is effective in preventing the recurrence of duodenal ulceration.     

四磨汤对妇科开腹术后胃肠运动功能的临床效应及安全性研究

目的：探讨四磨汤对妇科开腹术后胃肠运动功能的临床效应及安全性。方法：采用随机、双盲、安慰剂对照进行前瞻性研究，选取妇科开腹术后患者试验组79例，对照组66例。术后第1天，治疗组口服四磨汤口服液，对照组口服模拟四磨汤口服液。记录胃肠运动功能相关指标、生活质量积分、安全性检测指标、不良反应及有无并发症等，然后进行统计学分析。结果：与安慰剂对照组相比：治疗组术后首次肠鸣音恢复时间、首次肛门排气时间、首次排便时间平均分别缩短约9 h、7 h、8 h，治疗组对促进肠道运动的影响优于对照组。治疗组术后第4天生活质量评分明显升高，四磨汤对术后食欲、腹胀、睡眠改善有明显疗效。两组患者在安全性指标、并发症方面均无差异。结论：四磨汤能有效促进妇科开腹术后胃肠运动功能的恢复，减少输液量并改善患者生活质量，在妇科开腹术后患者中使用安全，无明显临床不良反应。     

七氟醚全麻复合硬膜外阻滞与镇痛对胸科手术应激反应的影响

目的观察评估七氟醚全麻复合硬膜外腔阻滞与镇痛对胸科手术应激激素和细胞因子的影响。方法选择20例开胸手术病人,随机分为两组,每组各10例,即全麻复合硬膜外腔阻滞组和全身麻醉组,分别测定麻醉诱导前、手术2、4h、术毕、术后1d及术后3d的血浆去甲肾上腺素、肾上腺素、血清促肾上腺皮质激素、皮质醇、C-反应蛋白、白细胞介素-6及白细胞介素-10的水平。结果血浆去甲肾上腺素和血清皮质醇全麻复合硬膜外腔阻滞组术中术后无显著改变,但全麻组术毕和术后1d显著升高(P<0.05),术后3d恢复至术前水平,组间比较前者有显著差异(P<0.05)。两组血浆肾上腺素、白细胞介素-10术中术后均无显著变化。两组血清促肾上腺皮质激素、白细胞介素-6及C-反应蛋白术中术后均显著升高(P<0.05),组间比较无显著差异(P>0.05)。结论硬膜外腔阻滞及术后硬膜外腔自控镇痛可以减轻胸部手术的应激反应。     

Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils

BACKGROUND: Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. OBJECTIVE: This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils. METHODS: We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD(30) ragweed nasal allergen challenge, patients received either omalizumab, approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD(30) dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. RESULTS: Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P <.001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group. CONCLUSIONS: Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells.     

Effect of omalizumab on adenosine 5'-monophosphate responsiveness in subjects with allergic asthma

BACKGROUND: The objective of this study was to evaluate the effects of omalizumab on bronchoconstriction induced by methacholine and adenosine 5'-monophosphate (AMP). METHODS: Thirty-four subjects with mild to moderate allergic asthma were randomized to receive placebo (n = 16) or omalizumab (n = 18) subcutaneously during 12 weeks. Airway responsiveness to AMP was measured at baseline and after 4 and 12 weeks of treatment, whereas the response to methacholine was measured at baseline and after 12 weeks of treatment. RESULTS: After 4 weeks of treatment, the increase in AMP PC(20) (provocative concentration required to produce a 20% fall in FEV(1)) was significantly greater in the omalizumab group than in the placebo group, the mean difference in the change between the groups being 1.52 doubling concentrations (95% CI, 0.25-2.79, p = 0.02). Compared with baseline, the mean AMP PC(20) values at 12 weeks were increased by 1.91 doubling concentrations with omalizumab (p < 0.001) and 1.01 doubling concentrations with placebo (p = 0.16), but changes were not significantly different between the treatment groups. Changes in methacholine PC(20) values were not significantly different between the omalizumab and placebo groups. CONCLUSIONS: In subjects with allergic asthma, omalizumab reduces the response to AMP without decreasing the response to methacholine. These findings are consistent with the conclusion that the contribution of IgE to the development of AMP bronchoconstriction is more important than their role in the induction of methacholine hyperresponsiveness.     

A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery

Previous studies have suggested that desmopressin may reduce the bleeding diathesis that often complicates open-heart surgery. To pursue this question further, we performed a double-blind, randomized, placebo-controlled trial to determine whether the previously reported beneficial effect of desmopressin on hemostasis during complex cardiac surgery was applicable to all elective cardiac surgical procedures involving cardiopulmonary bypass. In 150 consecutive patients, most of whom underwent primary coronary-artery bypass grafting, we compared the effects of intravenous desmopressin (0.3 microgram per kilogram of body weight) with those of saline placebo on postoperative blood loss and the need to replace blood products. The median amount of blood lost within the first 24 hours after operation was similar in the desmopressin and placebo groups (865 vs. 738 ml; P = 0.26). The postoperative use of blood replacement products did not differ significantly between the groups (1025 ml [95 percent confidence interval, 300 to 4140 ml] in the desmopressin group and 860 ml [247 to 5346 ml] in the placebo group). Desmopressin is believed to exert its hemostatic effect by releasing von Willebrand factor. The level of ristocetin cofactor, a functional index of the level of von Willebrand factor, was increased approximately twofold from base line in both treatment groups 90 minutes and 24 hours after the administration of medication. Similarly, the levels of von Willebrand factor multimers increased uniformly in both groups. These findings may be consistent with a normal stress response of von Willebrand factor to major surgery and could explain our failure to detect a therapeutic effect of desmopressin. We conclude that the majority of patients who undergo elective cardiac surgery receive no hemostatic benefit from the use of desmopressin.     

Vitamin E effects on nasal symptoms and serum specific IgE levels in patients with perennial allergic rhinitis.

BACKGROUND: Studies have shown that vitamin E intake may reduce IgE production. OBJECTIVE: To evaluate the effects of vitamin E supplementation on the severity of nasal symptoms and the serum levels of specific IgE in patients with perennial allergic rhinitis. METHODS: Sixty-three patients (mean +/- SD age, 12 +/- 2.4 years) with a history of perennial allergic rhinitis participated in this study. None of the patients had evidence of acute infectious disease or used tobacco, corticosteroids, antihistamines, or vitamins. Patients were randomized to receive either vitamin E (400 IU/d) or placebo for 4 weeks, with loratadine-pseudoephedrine (0.2/0.5 mg/kg) during the first 2 weeks of treatment. The severity of nasal symptoms was evaluated using a validated questionnaire, which was administered weekly for 4 weeks. The serum concentrations of specific IgE to 5 common inhalant allergens and lipid peroxides were measured before treatment and at the end of the study. RESULTS: Before, during, and after treatment, the symptom severity scores were similar in the 2 groups; within each group, a significant decrease was observed after the first week of follow-up (P < .05), with no further changes. Serum levels of specific IgE and lipid peroxides did not show any significant changes related to vitamin E intake within and between groups. CONCLUSIONS: In patients with perennial allergic rhinitis, vitamin E supplementation (400 IU/d) did not have any significant effects on nasal symptom severity or on serum concentrations of specific IgE to 5 common allergens.     

Clinical efficacy of microencapsulated timothy grass pollen extract in grass-allergic individuals.

BACKGROUND: Conventional allergen immunotherapy is clinically effective in reducing the symptoms of allergic rhinitis and asthma. It differs from other pharmacotherapies in that it can induce long-term clinical remission of these diseases. However, it requires years of treatment and is associated with serious allergic reactions. OBJECTIVE: To evaluate the safety, clinical efficacy, and immunologic mechanisms of immunotherapy with an oral, microencapsulated form of timothy grass allergen. METHODS: In this double-blind, placebo-controlled study, 24 patients aged 19 to 55 years with grass pollen allergy were randomized to receive either microencapsulated timothy grass pollen extract or placebo once a day for 10 weeks. The dose of study drug was doubled weekly. Safety was evaluated through weekly visits, daily symptom diaries, and routine laboratory tests. Efficacy was evaluated by comparing medication use and symptoms scores during peak grass pollen season before and after treatment. Allergen-specific T-cell responses, cytokine production, and IgG, IgE, and skin reactivity were measured to evaluate immunologic mechanisms. RESULTS: Eleven of 12 patients in the active treatment group had a decrease in the combined medication and symptom score, but only 4 of 10 patients in the placebo group had a decrease in scores. The proliferative response to timothy grass was reduced by at least 30% in 9 of the 12 grass-treated patients, but only 3 of 11 placebo patients had a proliferative response reduction. Timothy grass-induced interleukin-5 messenger RNA was reduced in the active group, but not in the placebo group. There were no significant changes in either group in IgG, IgE, and skin reactivity. CONCLUSIONS: Oral immunotherapy with microencapsulated allergen induces a form of immunologic tolerance to the allergen and is a safe, efficient, and effective method of allergen immunotherapy.     

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

Background: Anti‐IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti‐IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti‐IgE on allergen‐induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double‐blind, placebo‐controlled study. Methods: Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti‐IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC₂₀) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC₂₀, inflammatory cells in biopsies and sputum were assessed. Results: Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti‐IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4–0.5%) and postallergen biopsies (15–2 cells/0.1 mm²) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high‐affinity IgE receptor and CD4+ cells were decreased within the anti‐IgE group. There were no significant differences for PC₂₀ methacholine. Conclusion: The response to inhaled allergen in asthma is diminished by anti‐IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE‐bearing cells postallergen without changing PC₂₀ methacholine. This suggests that the benefits of anti‐IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE‐bearing cells.     

Effects on inflammation parameters of a double-blind,placebo controlled one-year course of SLIT in children monosensitized to mites

BACKGROUND: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor. METHODS: Twenty-four children (age range 4-16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double-blind, placebo-controlled design. Before treatment and 10-12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite-specific IgE (sIgE), allergen-specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT. RESULTS: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group. CONCLUSIONS: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.     

Specific IgE serum concentration is associated with symptom severity in children with seasonal allergic rhinitis

Background: The impact of allergen‐specific and total IgE serum levels before and during the pollen season on symptom severity as well as efficacy of treatment with anti‐IgE requires further delineation. Methods: Birch and grass pollen allergic patients aged 6–17 years with seasonal allergic rhinitis (SAR) were analyzed for the association of IgE serum concentration with symptom severity and rescue medication use (combination: symptom load, SL) during the grass pollen season. Reference group A (n = 53) received placebo, while group B (n = 54) received Omalizumab (anti‐IgE) monotherapy before and during the grass pollen season. Results: Patients on placebo with high baseline specific grass pollen IgE (>50 kU/l) had a significantly higher SL compared with those with low IgE levels (≤50 kU/l): SL 1.28 vs 0.61, P = 0.015. This association was nonexistent in patients treated with anti‐IgE. In contrast, baseline total IgE levels did not correlate with SL in any group. Patients with anti‐IgE treatment and high free total IgE levels (>16.7 ng/ml) had a significantly higher SL compared with those with low free total IgE levels (≤16.7 ng/ml): SL 0.63 vs 0.23, P = 0.031. Conclusions: Baseline specific IgE, but not total IgE, is associated with symptom severity during the pollen season in children with SAR. Likewise, the symptom load in SAR patients with anti‐IgE correlates with free total IgE levels. Although further research in larger populations is needed to confirm our findings, our data suggest that specific IgE can be used as a parameter for patient selection for this kind of treatment.     

Postoperative sleep disturbance: influences of opioids and pain in humans

STUDY OBJECTIVES: To test the hypothesis that opioids and pain contribute independently to postoperative sleep disturbance, 10 women undergoing surgery requiring a low abdominal incision for treatment of benign gynecologic conditions were randomized to receive either epidural opioid (fentanyl) (n=6) or epidural local anesthetic (bupivacaine) (n=4) for intraoperative and postoperative analgesia. DESIGN: N/A SETTING: N/A PATIENTS OR PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS: Polysomnography was performed in a standard patient room on the preoperative and first three postoperative nights. Pain at rest and with coughing was evaluated using a visual-analogue pain scale each evening and morning. RESULTS: On the first postoperative night, rapid eye movement (REM) sleep was abolished in all patients. On the third postoperative night, the mean +/- SE REM sleep time increased significantly (p=.003) to 9.8% +/- 3.1% in the fentanyl group, and 12.9% +/- 3.8% in the bupivacaine group. Conversely, light non-REM (NREM) sleep (%stage 1 + %stage 2) was higher on the first postoperative night and significantly lower on the third postoperative night (p=0.011). Between group comparison revealed only that the mean % slow-wave sleep (SWS) in the fentanyl group (6.0%, 2.0%, and 14.7%) was different from the bupivacaine group (7.8%, 9.1%, and 10.6%) in the postoperative period after adjusting for the preoperative night % SWS (p=0.021). Pain was well controlled in all patients, but was slightly better controlled in the fentanyl group than in the bupivacaine group on postoperative night 2 (p=0.024). There was no statistically significant association between pain score and any polysomnographically defined stage. CONCLUSION: Postoperative patients suffer a profound sleep disturbance even when opioids are avoided and pain is well controlled.     

A randomized, double-blind trial of the effect of treatment with formoterol on clinical and inflammatory parameters of asthma in children.

BACKGROUND: In addition to their bronchodilating effect, long-acting inhaled beta-agonists have recently been shown to have some anti-inflammatory properties. OBJECTIVE: The purpose of this study was to evaluate the effect of formoterol on inflammatory mediators in children. METHODS: In this double-blind, randomized, placebo-controlled trial, 34 children, aged 6 to 18 years, with moderate atopic asthma, were randomly allocated to receive formoterol or matching placebo for 4 weeks. The primary endpoint of this study was to determine changes in serum levels of inflammatory markers after treatment with formoterol; secondary endpoints included clinical efficacy and bronchial hyperreactivity. The following parameters were measured: symptom score, forced expiratory volume in 1 second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) for histamine and peripheral blood eosinophil count, serum levels of eosinophil cationic protein (ECP), soluble receptor of interleukin-2 (sIL-2R), level of interleukin-4 (IL-4), level of soluble intercellular adhesion molecule-1 (ICAM-1), and immunoglobulin E (IgE) level before and after treatment. RESULTS: Compared with placebo, treatment with formoterol significantly improved lung function. The mean value of FEV1 changed from 74% of predicted value before treatment to 80% of predicted value after treatment (P < 0.001). The mean concentration of eosinophil blood count before and after treatment was 379 and 310 cells/mm3 (P = 0.035); ECP was 93 and 83 mcg/L; and serum IL-4 was 0.13 and 0.11 pg/mL (P = 0.001). There was no significant difference between formoterol and placebo recipients in PC20H, and serum concentration of sIL-2R, sICAM-1, or IgE after treatment. The group that received formoterol showed improvement in pulmonary function as measured by FEV1 (P < 0.001), and PC20H (P = 0.04) after 4 weeks of treatment. These patients also showed improvement of clinical symptoms (P < 0.001). Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count, ECP, and IL-4, but there was no difference in before and after measurements of sIL-2R, sICAM-1, and IgE. CONCLUSIONS: These results indicate that formoterol has measurable anti-inflammatory properties and can diminish asthma symptoms and bronchial hyperreactivity.