Cytokine Profiles of Stimulated Blood Lymphocytes in Asthmatic and Healthy Adolescents Cross the School Year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-γ (IFN-γ), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th 1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-γ:IL-4 and IFN-γ:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation

Soybean Oil Is Not Allergenic to Soybean-Sensitive Individuals

We have previously demonstrated that peanut oil is not allergenic to peanut-sensitive individuals. Seven soybean-sensitive patients were enrolled in a double-blind crossover study to determine whether ingestion of soybean oil can induce adverse reactions in such patients. All subjects had histories of systemic allergic reactions (urticaria, angioedema, wheezing, dyspnea, and/or vomiting) after soybean ingestion and had positive puncture skin tests with a 1:20 w/v glycerinated-saline whole soybean extract. Sera from six of the seven subjects were tested by RAST assay for the presence of specific IgE antibodies to soybean allergens. All patients had elevated levels of serum IgE antibodies to the crude soybean extract; binding values ranged from 2.3 to 28.1 times that of a negative control serum. Before the oral challenges, all patients demonstrated negative puncture skin tests to three commercially available soybean oils and to olive oil (control). On four separate days, patients were challenged with the individual soybean oils and to olive oil in random sequence. At 30-minute intervals, under constant observation, patients ingested 2, 5, and 8 ml of one of the soybean oils or olive oil contained in 1 ml capsules. No untoward reactions were observed with either the commercially available soybean oils or olive oil. Soybean oil ingestion does not appear to pose a risk to soybean-sensitive individuals

Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study

BACKGROUND: This study examined the attitudes and actions of 3415 physician-recruited adults aged ≥ 16 years with asthma in eleven countries who were prescribed regular maintenance therapy with inhaled corticosteroids or inhaled corticosteroids plus long-acting β(2)-agonists. METHODS: Structured interviews were conducted to assess medication use, asthma control, and patients' ability to recognise and self-manage worsening asthma. RESULTS: Despite being prescribed regular maintenance therapy, 74% of patients used short-acting β(2)-agonists daily and 51% were classified by the Asthma Control Questionnaire as having uncontrolled asthma. Even patients with well-controlled asthma reported an average of 6 worsenings/year. The mean period from the onset to the peak symptoms of a worsening was 5.1 days. Although most patients recognised the early signs of worsenings, the most common response was to increase short-acting β(2)-agonist use; inhaled corticosteroids were increased to a lesser extent at the peak of a worsening. CONCLUSION: Previous studies of this nature have also reported considerable patient morbidity, but in those studies approximately three-quarters of patients were not receiving regular maintenance therapy and not all had a physician-confirmed diagnosis of asthma. This study shows that patients with asthma receiving regular maintenance therapy still have high levels of inadequately controlled asthma. The study also shows that patients recognise deteriorating asthma control and adjust their medication during episodes of worsening. However, they often adjust treatment in an inappropriate manner, which represents a window of missed opportunity

Prevalence of Sensitivity to Sulfiting Agents in Asthmatic Patients

Ingestion of sulfiting agents can induce wheezing in some asthmatic patients. However, neither the prevalence of sulfite sensitivity nor the clinical characteristics of the affected asthmatic population are known. In a prospective single-blind screening study, 120 non-steroid-dependent and 83 steroid-dependent asthmatic patients underwent challenge with oral capsules of potassium metabisulfite. Five non-steroid-dependent and 16 steroid-dependent asthmatic patients experienced a greater than 20 percent reduction in their one-second forced expiratory volume within 30 minutes following the oral challenge. Twelve of these sulfite reactors were rechallenged with metabisulfite capsules in a double-blind protocol. Under these conditions, only three of seven steroid-dependent patients had a positive response. Moreover, only one of five non-steroid-dependent patients had a response to double-blind challenge. On the basis of this challenge study, the best estimate of the prevalence of sulfite sensitivity in the asthmatic patients studied is 3.9 percent. This population, however, contained a larger number of steroid-dependent asthmatic patients than would be found in the general asthmatic population. It is concluded, therefore, that the prevalence of sulfite sensitivity in the asthmatic population as a whole would be less than 3.9 percent and that steroid-dependent asthmatic patients are most at risk

Halococcus salifodinae sp. nov., an Archaeal Isolate from an Austrian Salt Mine

A novel extremely halophilic archaeon (archaebacterium) was isolated from rock salt obtained from an Austrian salt mine. The deposition of the salt is thought to have occurred during the Permian period (225 x 106 to 280 x 10(exp 6) years ago). This organism grew over a pH range of 6.8 to 9.5. Electron microscopy revealed cocci in tetrads or larger clusters. The partial 16S rRNA sequences, polar lipid composition, and menaquinone content suggested that this organism was related to members of the genus Halococcus, while the whole-cell protein patterns, the presence of several unknown lipids, and the presence of pink pigmentation indicated that it was different from previously described coccoid halophiles. We propose that this isolate should be recognized as a new species and should be named Halococcus salifodinae. The type strain is Bl(sub p) (= ATCC 51437 = DSM 8989). A chemotaxonomically similar microorganism was isolated from a British salt mine

Hymenobacter artigasi sp. nov., isolated from air sampling in maritime Antarctica

A rod-shaped and Gram-stain-negative bacterial strain, 1BT, was isolated from an air sample collected at King George Island, maritime Antarctica. Strain 1BT is strictly aerobic, psychrophilic, catalase-positive, oxidase-positive and non-motile. Growth of strain 1BT is observed at 0–20 °C (optimum, 10 °C), pH 6.0–8.0 (optimum, pH 8.0) and in the presence of 0–1.0% NaCl (optimum, 0.5 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequences places strain 1BT within the genus Hymenobacter and shows the highest similarity to Hymenobacter antarcticus VUG-A42aaT (97.5 %). The predominant menaquinone of strain 1BT is MK-7 and the major fatty acids (>10 %) comprise summed feature 3 (C16 : 1  ω7c and/or C16 : 1  ω6c; 32.5 %), iso-C15 : 0 (17.6 %) and anteiso C15 : 0 (12.3 %). The polar lipid profile consists of the major compounds phosphatidylethanolamine, phosphatidylserine, two unidentified aminolipids and one unidentified phospholipid. The DNA G+C content based on the draft genome sequence is 61.2 mol%. Based on the data from the current polyphasic study, 1BT represents a novel species of the genus Hymenobacter , for which the name Hymenobacter artigasi sp. nov. is suggested. The type strain is 1BT (=CCM 8970T=CGMCC 1.16843T)

Sensitivity to Sulfited Foods among Sulfite-Sensitive Subjects with Asthma

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction

The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype

We previously demonstrated inhibition of ovalbumin (OVA)-induced allergic airway hyper-responsiveness in the mouse using ES-62, a phosphorylcholine-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae. This inhibition correlated with ES-62-induced mast cell desensitisation, although the degree to which this reflected direct targeting of mast cells remained unclear as suppression of the Th2 phenotype of the inflammatory response, as measured by eosinophilia and IL-4 levels in the lungs, was also observed. We now show that inhibition of the lung Th2 phenotype is reflected in ex vivo analyses of draining lymph node recall cultures and accompanied by a decrease in the serum levels of total and OVA-specific IgE. Moreover, ES-62 also suppresses the lung infiltration by neutrophils that is associated with severe asthma and is generally refractory to conventional anti-inflammatory therapies, including steroids. Protection against Th2-associated airway inflammation does not reflect induction of regulatory T cell (Treg) responses (there is no increased IL-10 or Foxp3 expression) but rather a switch in polarisation towards increased T-bet expression and IFNγ production. This ES-62-driven switch in the Th1/Th2 balance is accompanied by decreased IL-17 responses, a finding in line with reports that IFNγ and IL-17 are counter-regulatory. Consistent with ES-62 mediating its effects via IFNγ-mediated suppression of pathogenic Th2/Th17 responses, we found that neutralising anti-IFNγ antibodies blocked protection against airway inflammation in terms of pro-inflammatory cell infiltration, particularly by neutrophils and lung pathology. Collectively, these studies indicate that ES-62, or more likely small molecule analogues, could have therapeutic potential in asthma, in particular for those subtypes of patients (e.g. smokers, steroid-resistant) who are refractory to current treatments

Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial

Abstract Background Many patients with asthma require frequent rescue medication for acute symptoms despite appropriate controller therapies. Thus, determining the most effective relief regimen is important in the management of more severe asthma. This study’s objective was to evaluate whether ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI) provides more effective acute relief of bronchospasm in moderate-to-severe asthma than albuterol hydrofluoroalkaline (ALB-HFA) alone after 4 weeks. Methods In this double-blind, crossover study, patients who had been diagnosed with asthma for ≥1 year were randomized to two sequences of study medication “as needed” for symptom relief (1–7 day washout before second 4-week treatment period): CVT-MDI/ALB-HFA or ALB-HFA/CVT-MDI. On days 1 and 29 of each sequence, 6-hour serial spirometry was performed after administration of the study drug. Co-primary endpoints were FEV 1 area under the curve (AUC 0–6 ) and peak (post-dose) forced expiratory volume in 1 s (FEV 1 ) response (change from test day baseline) after 4 weeks. The effects of “as needed” treatment with ALB-HFA/CVT-MDI were analyzed using mixed effect model repeated measures (MMRM). Results A total of 226 patients, ≥18 years old, with inadequately controlled, moderate-to-severe asthma were randomized. The study met both co-primary endpoints demonstrating a statistically significant treatment benefit of CVT-MDI versus ALB-HFA. FEV 1 AUC 0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI (p <0.0001); peak FEV 1 response was 357 ml for ALB-HFA, 434 ml for CVT-MDI (p <0.0001). Adverse events were comparable across groups. Conclusions CVT-MDI significantly improved acute bronchodilation over ALB-HFA alone after 4 weeks of “as-needed” use for symptom relief, with a similar safety profile. This suggests additive bronchodilator effects of β 2 -agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma. Trial registration ClinicalTrials.gov No.: NCT00818454; Registered November 16, 2009

The Effect of Subcutaneous German Cockroach Immunotherapy (SCIT) on Nasal Allergen Challenge (NAC) and Cockroach-specific Antibody Responses Among Urban Children and Adolescents

Rationale: Cockroach allergy contributes to asthma and rhinitis morbidity among many urban children. Treatment with cockroach SCIT could be beneficial. Methods: 8-17 year-old children with mild-moderate asthma from 11 urban sites participated in a randomized double-blind placebo-controlled SCIT trial using non-standardized, glycerinated German cockroach extract. Positive cockroach skin tests, cockroach-specific IgE, and nasal challenge response with total nasal symptom scores (TNSS) ≥6 or maximal sneeze scores of 3 during a graded NAC were required for enrollment. Following dose escalation, 0.4 ml of undiluted extract was targeted for maintenance dosing (∼7 mcg Bla g2/dose). The primary endpoint was change in NAC-induced mean TNSS from baseline to one year post randomization. Changes in cockroach-specific IgE (CRsIgE) and IgG4 (CRsIgG4) were also analyzed. Results: Mean TNSS did not significantly change from baseline in either group (placebo n=29, SCIT n=28). There was no significant difference in the change in mean TNSS between placebo and SCIT [−0.79±0.35 vs. −1.02±0.37, respectively, difference=0.2(−1.15, 0.70), p=0.63]. Baseline CRsIgE and CRsIgG4 didn’t differ between groups. Mean CRsIgE decreased in both groups following treatment: 3.6 to 2.3 kU/L (0.64 fold change), p=0.015 and 8.3 to 4.2 kU/L (0.51 fold change), p\u3c0.001 in placebo and SCIT respectively, but did not differ between groups [p=0.33]. Significant increases in CRsIgG4 post-treatment were observed among SCIT recipients only: 0.07 to 12.3 mg/L (176 fold change), p\u3c0.001. Conclusions: Cockroach SCIT increased CRsIgG4 levels but did not significantly alter NAC-induced TNSS responses. The extent to which NAC in these children may reflect clinical efficacy for rhinitis or asthma is uncertain