Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Architecture of crossed-lamellar bivalve shells: the southern giant clam (Tridacna derasa, Röding, 1798).

Tridacna derasa shells show a crossed lamellar microstructure consisting of three hierarchical lamellar structural orders. The mineral part is intimately intergrown with 0.9 wt% organics, namely polysaccharides, glycosylated and unglycosylated proteins and lipids, identified by Fourier transform infrared spectrometry. Transmission electron microscopy shows nanometre-sized grains with irregular grain boundaries and abundant voids. Twinning is observed across all spatial scales and results in a spread of the crystal orientation angles. Electron backscatter diffraction analysis shows a strong fibre texture with the [001] axes of aragonite aligned radially to the shell surface. The aragonitic [100] and [010] axes are oriented randomly around [001]. The random orientation of anisotropic crystallographic directions in this plane reduces anisotropy of the Young's modulus and adds to the optimization of mechanical properties of bivalve shells.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Improved recombinant Api m 1- and Ves v 5-based IgE testing to dissect bee and yellow jacket allergy and their correlation with the severity of the sting reaction.

BACKGROUND: No study has assessed the diagnostic sensitivity of rApi m 1 and rVes v 5 on Immulite testing system. OBJECTIVE: To compare the diagnostic sensitivity of commercially available venom recombinant allergens between the currently available immunoassays [ImmunoCAP (CAP) and Immulite (LITE)] and establish their correlation with the severity of the sting reaction. METHODS: This study evaluated 95 bee venom and 110 yellow jacket venom-allergic subjects. We measured the levels of sIgE to rApi m 1, rVes v 5 (LITE and CAP), rApi m 2 (LITE), rVes v 1 (CAP) and total IgE (CAP). Forty-nine healthy subjects served as controls. RESULTS: The diagnostic sensitivity of rApi m 1 and rVes v 5 was significantly higher with the LITE than with the CAP system (71% vs. 88% and 82% vs. 93%). The specificity of both assays for both allergens was between 94% and 98%. Twenty-nine patients that tested negative for rApi m 1 or rVes v 5 with CAP were positive with LITE, but none of the patients that tested negative with LITE were positive with CAP. The positive values of rApi m 1 and rVes v 5 were on average 2.7 and 2.3 times higher, with the LITE than with the CAP system. The combination of rApi m 1 and rApi m 2 (LITE) and the combination of rVes v 5 (LITE) and rVes v 1 (CAP) almost matched the sensitivity of native venoms (95% and 97%, respectively), whereas the diagnostic sensitivity of the combination of rVes v 5 and rVes v 1 (CAP) did not reach the sensitivity of rVes v 5 (LITE) alone (90% vs. 93%). IgE levels to venom recombinants and total IgE did not correlate with the severity of sting reaction. CONCLUSIONS & CLINICAL RELEVANCE: The use of rApi m 1 and rVes v 5 with the LITE system significantly enhanced diagnostic utility of venom recombinants and should improve the dissection of bee and yellow jacket venom allergy.

Immunological and clinical factors associated with adverse systemic reactions during the build-up phase of honeybee venom immunotherapy.

BACKGROUND: Adverse systemic reactions (SRs) are more common in honeybee venom immunotherapy (VIT) than in wasp VIT. Factors that might be associated with SRs during the honeybee VIT are poorly understood. OBJECTIVE: Our aim was to evaluate risk factors for SRs during the build-up phase of honeybee venom immunotherapy. METHODS: We included 93 patients who underwent ultra-rush honeybee VIT. The adverse SRs and their severity was compared to various immunological (sIgE, tIgE, basophil CD63 response, baseline tryptase, and skin tests), patient-specific (age, sex, cardiovascular conditions and medications, and other allergic diseases), and sting-specific factors (anaphylaxis severity, time interval to onset of symptoms, and absence of cutaneous symptoms). RESULTS: Twenty-three patients (24.7%) experienced mild SRs and 13 patients (14%) severe SRs. In five patients with severe SRs, the build-up was stopped. High basophil allergen sensitivity, evaluated as dose-response curve metrics of EC15, EC50, CD-sens, AUC, or the response to submaximal 0.01 µg/mL of venom concentration, was the most significant risk factor and only independent predictor of severe SRs and/or build-up stop. Time interval of <5 min after sting to onset of symptoms and lower specific IgEs to rApi m1 was also associated with severe SRs. There was no difference in other immunological, patient-specific, or sting-specific factors, including the baseline tryptase. None of the studied factors was associated with mild SRs. CONCLUSION AND CLINICAL RELEVANCE: High basophil allergen CD63 sensitivity phenotype was a major indicator of severe adverse SRs during the build-up phase of honeybee VIT. Possibly role was also showed for short latency to filed sting reaction and low sIgE to rApi m1. Before honeybee VIT, measurement of basophil allergen sensitivity should be used to identify patients with a high risk for severe side-effects.

Sustained effect of grass pollen subcutaneous immunotherapy on suppression of allergen-specific basophil response; a real-life, nonrandomized controlled study.

BACKGROUND: An important advantage of allergen immunotherapy as compared to pharmacotherapy for allergic rhinitis is the long-term effect that persists after completing immunotherapy. The mechanism of the sustained effect of allergen immunotherapy is not completely understood. METHODS: We conducted a 7-year study of monitoring allergen-specific basophil response and serological markers in 20 subjects with moderate-to-severe grass pollen-allergic rhinitis just before beginning and after up-dosing of subcutaneous grass pollen immunotherapy, before the first pollen season, and 1-2 years after completion of 3-5 years of treatment. Comparable untreated rhinitis subjects were followed at the same time points. Clinical outcomes included assessment of symptoms, use of rescue medication, and quality of life. The basophil response was also monitored after removal of IgG antibodies. RESULTS: Basophil response assessed as area under the curve (AUC) halved during initiation of SCIT and was 55% lower 1-2 years after completing SCIT. In the untreated group, the basophil response remained comparable. Although immunotherapy-induced grass pollen-specific IgG4 levels decreased to near pre-immunotherapy levels after completing SCIT, the removal of IgG antibodies resulted in an increase in basophil response almost to the pre-immunotherapy levels. In untreated subjects, removal of IgG did not have any effect on basophil response. CONCLUSIONS: Grass pollen immunotherapy induces sustained suppression of the allergen-specific basophil response that persists after completion of treatment and could account for long-term clinical tolerance. It also seems to be associated with persistent blocking activity of IgG antibodies.

A polymorphism in ORMDL3 is associated not only with asthma without rhinitis but also with chronic obstructive pulmonary disease.

BACKGROUND: Asthma is a heterogeneous disease, and asthmatic patients without rhinitis more commonly have fixed airway obstruction, a feature that is also typical of chronic obstructive pulmonary disease (COPD). The Dutch hypothesis suggests that both COPD and asthma have common genetic risk factors. The purpose of this study was to assess the association between the polymorphism rs4795405 in the known asthma candidate gene ORMDL3 and asthma with and without rhinitis. We also analyzed COPD in order to investigate whether, in addition to a clinical overlap, there might also be a genetic overlap between COPD and asthma. METHODS: The population of this genetic association study comprised 493 Slovenian adults, distributed as follows: 131 patients with asthma (59 had asthma with rhinitis and 72 asthma without rhinitis), 59 patients with rhinitis only, 133 patients with COPD, and 170 controls. Genotypes for rs4795405 were determined using the TaqMan genotyping assay. RESULTS: rs4795405 was specifically associated with asthma without rhinitis. Assuming a recessive genetic model, we found the CC genotype in 26% of healthy controls, in 24% of patients with asthma with rhinitis (P = .862), and in 44% of patients with asthma without rhinitis (P = .006). Polymorphism rs4795405 was also associated with COPD, for which the CC genotype was found in 37% of cases (P = .045). CONCLUSIONS: rs4795405 was strongly associated with asthma without rhinitis, a subtype of asthma for which a higher degree of airway obstruction was found. These results show the importance of analyzing different asthma phenotypes in genetic association studies. We also observed a genetic overlap between COPD and asthma without rhinitis.

Short-term venom immunotherapy induces desensitization of FcεRI-mediated basophil response.

BACKGROUND: The precise immunological mechanisms for the early clinical protection of venom immunotherapy (VIT) have not yet been explained. Our aim was to evaluate whether high-affinity IgE receptor (FcεRI) and the related basophil function have a role in the induction of short-term VIT protection. METHODS: We included 60 adults and 48 children. Basophil threshold sensitivity (CD-sens) to anti-FcεRI stimulation, and FcεRI gene and cell-surface expression were assessed at the beginning and just before the first maintenance dose (MD) of 100 µg of ultra-rush VIT (day 5) and at the beginning, during buildup, and just before the first MD of 70 µg and of 100 µg of semi-rush VIT (weeks 1-2 and 5). RESULTS: We demonstrated a significant reduction in CD-sens to anti-FcεRI stimulation before the first MD in both ultra-rush and semi-rush VIT in all included subjects. FcεRI gene and/or cell-surface expression was decreased in 34-100% of subjects, with different dynamics between VIT protocols. CONCLUSION: We found a marked desensitization of FcεRI-activated basophils after short-term VIT. This suppression, which could be highly relevant for the development of early protective mechanisms, might be also related to the changes at the level of FcεRI expression.

High non-specific T lymphocyte response to the adjuvanted H1N1 vaccine in comparison with the H1N1/H3N2/B-Brisbane vaccine without adjuvant.

Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non-adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non-specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1-specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 µg of H1N1 and squalene-based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non-adjuvanted influenza vaccine (15 µg of each: H1N1, H3N2, and B-Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1-induced immunogenicity was good for both vaccines. Our results suggest a pronounced non-specific T cell response after AS03-adjuvanted 2009 H1N1 vaccination.

Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients treated with chemotherapy.

PURPOSE: Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes. PATIENTS AND METHODS: This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy. To determine the ABCB1 genotype, allelic specific TaqMan(®) probes were used in a RT-PCR . RESULTS: Patients carrying the G2677T/A TT + TA + AA genotypes (24 %) or the C3435T CT + TT genotypes (72 %) or the 2677T/A-3435T haplotype (40 %) had a longer PFS (Cox regression, P = 0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P = 0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT + TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P = 0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P = 0.051), but its independent value was not confirmed (Cox regression, P = 0.071). CONCLUSIONS: Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.

Basophil response and the induction of a tolerance in venom immunotherapy: a long-term sting challenge study.

BACKGROUND: There is no in vitro test to predict the induction of long-term tolerance in patients treated with venom immunotherapy (VIT). The aim of this study was to investigate whether immunotherapy-induced changes in basophil responsiveness reflect a state of protection and the induction of a tolerance. METHODS: Twenty-three patients with allergic reaction after Hymenoptera sting (11 wasp and 12 honeybee) were treated with VIT. In all patients, a CD63 basophil activation test was performed before the beginning of immunotherapy, after 1 year and after completing 4-6.5 years of immunotherapy (approximately 1 year after stopping). The tolerance was then evaluated by a sting challenge test. The basophil activation test was repeated 3-6 months after the challenge. RESULTS: Twenty-two subjects showed a negative sting challenge, and one subject, a positive sting challenge. Allergen-specific basophil response remained unchanged after 1 year of immunotherapy. However, after immunotherapy, a significant and approximately fourfold decrease was demonstrated in all tolerant subjects mainly in response to submaximal 0.1 µg/ml allergen concentration. This depression was sustained and did not change with the sting challenge test. In a nontolerant patient with a positive sting challenge, basophil response did not change. CONCLUSIONS: Our results suggest that the depression of allergen-specific basophil response seems to be associated with the induction of a tolerance after completing a course of VIT.

Rhinitis symptoms caused by grass pollen are associated with elevated basophile allergen sensitivity and a larger grass-specific immunoglobulin E fraction.

BACKGROUND: The mechanisms responsible for the difference between clinically irrelevant IgE-sensitization and allergic rhinitis are not fully understood. OBJECTIVE: We evaluated the humoral and cellular mechanisms that may be associated with the presence of allergic rhinitis symptoms. METHODS: We selected 26 subjects with positive grass pollen skin tests and IgE antibodies to Timothy (g6) and the major grass allergens rPhl p 1, 5b. Fourteen of those patients reported a history of allergic rhinitis. During winter, we performed a grass pollen CD63 basophile activation test using four log allergen concentrations, followed by a grass nasal provocation test (NPT). We obtained symptom scores in the subsequent pollination season. RESULTS: We showed that subjects with a positive NPT have significantly higher CD63 basophile grass pollen responsiveness than NPT-negative subjects, preferably at submaximal allergen concentrations, which represent cellular sensitivity. Moreover, basophile sensitivity positively correlated with the size of the grass-specific IgE fraction in relation to total IgE, and it was highly predictive of allergic rhinitis symptoms in the following pollination season. CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis symptoms are significantly associated with allergen-specific basophile sensitivity. In vitro evaluation of basophile sensitivity should prove useful for distinguishing clinical phenotype of allergic sensitization.

Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma.

Asthma is one of the most common chronic diseases in childhood. It is well known that genetic variability contributes to asthma risk. One of the most replicated asthma candidate genes is ORM1-like 3 (Saccharomyces cerevisiae) (ORMDL3), which has been associated with childhood asthma susceptibility. Another asthma candidate gene is signal transducer and activator of transcription 6 (STAT6), a regulator of IgE class switching. Gene coding thromboxane A2 receptor (TBXA2R), involved in chronic airway inflammation, has been associated with asthma in several genetic studies. We have studied the association of polymorphism rs4795405 in ORMDL3, rs324011 in STAT6 as well as rs8113232 and rs3786989 in TBXA2R with asthma risk, various asthma phenotypes and asthma-related symptoms. The study group consisted of 154 children with asthma, in whom clinical parameters were measured and whose asthma control and atopic status were determined. A control group comprised 71 healthy children. Genotyping was performed using an allelic discrimination assay. The ORMDL3 polymorphism rs4795405 was suggestively associated with asthma risk. Furthermore, it was significantly associated with nonatopic asthma and asthma without rhinitis. No association was detected between the STAT6 polymorphism rs324011 or the TBXA2R polymorphisms rs8113232 and rs3786989 and asthma susceptibility. However, an association between rs324011 in STAT6 with recurrent wheezing in early childhood and a suggestive association between rs8113232 in TBXA2R with rhinitis in children with asthma were observed. Our results confirmed ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms were not associated with asthma risk, but they were associated with asthma-related symptoms.

Airway angiogenesis in stable and exacerbated chronic obstructive pulmonary disease.

Angiogenesis is a prominent feature of structural tissue remodelling that occurs in chronic airway diseases, including chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the airway levels of VEGF, angiogenin, IL-8 and TNF-α in patients with COPD during the stable phase and during acute exacerbation of the disease. We analysed induced sputum samples from 28 patients with COPD. Thirteen of these patients were followed up and second samples of sputum were obtained during acute exacerbation of the disease. The two control groups consisted of 12 healthy smokers and seven healthy non-smokers, all with normal lung function tests. Concentrations of VEGF, angiogenin, IL-8, TNF-α and bFGF were measured by cytometric bead array. In the induced sputum of patients with stable COPD, concentrations of VEGF (P < 0.001, P = 0.02), angiogenin (P < 0.0001, P < 0.0001), IL-8 (P < 0.0001, P = 0.0021) and TNF-α (P < 0.001, P = 0.03) were significantly elevated in comparison with healthy smokers and non-smokers. No additional elevation of angiogenic factors was demonstrated at the time of exacerbation. There was a significant negative correlation between FEV1 and VEGF (P < 0.05, r = -0.38), angiogenin (P < 0.0001, r = -0.68) and IL-8 (P < 0.001, r = -0.54) among smokers (smoking COPD patients and healthy smokers). No significant differences were observed between groups of healthy smokers and non-smokers. These results showed increased airway angiogenesis in patients with COPD. Moreover, VEGF, IL-8 and angiogenin negatively correlated with pulmonary function, which suggests their important role in COPD airway remodelling. However, no additional angiogenic activation was found during exacerbation of COPD.

Anxiety and depression during hospital treatment of exacerbation of chronic obstructive pulmonary disease.

This study investigated the prevalence, risk factors and rate of recognition of anxiety and depression in 50 patients hospitalized for exacerbation of chronic obstructive pulmonary disease (COPD). Using the Primary Care Evaluation of Mental Disorders questionnaire, 13 patients were identified as having depression, four had anxiety and eight had a combination of the two. Patients with anxiety and/or depression had a significantly higher partial pressure of oxygen and pH, and a lower partial pressure of carbon dioxide, in arterial blood on admission, more severe dyspnoea after a 6-min walk test and less improvement of dyspnoea from admission to discharge than COPD patients without anxiety and/or depression. Two patients were referred to a mental health specialist during their hospitalization, indicating a low rate of recognition. The results suggest that patients with mental disorders are referred and admitted to hospital earlier in the course of a COPD exacerbation due to earlier and more intense perception of dyspnoea.

Immunoglobulin G-dependent changes in basophil allergen threshold sensitivity during birch pollen immunotherapy.

BACKGROUND: The effects of pollen immunotherapy on effector cells of allergic inflammation, such as mast cells and basophils, are poorly understood. OBJECTIVE: For this reason, we conducted an open study on basophil allergen threshold sensitivity during birch pollen immunotherapy. METHODS: Basophil sensitivity was measured by CD63 flow cytometry in 14 patients with moderate-severe intermittent birch pollen rhinitis using four log allergen concentrations. In nine patients, we analysed the basophil sensitivity before and during treatment with subcutaneous birch immunotherapy (perennial scheme with allergoid). We also included eight birch-allergic donor subjects for IgG inhibition experiments and eight control subjects. RESULTS: There was a decrease in basophil allergen threshold sensitivity after 2, 3, and 5 months of immunotherapy. This decrease was correlated with an improvement in patients' symptoms measured on a visual analogue scale. The serum obtained after immunotherapy induced a significant decrease in allergen threshold sensitivity in donor birch-allergic basophils. This inhibition was not observed after IgG depletion from the serum. CONCLUSIONS: In this study, we showed that birch immunotherapy-induced IgG antibodies are associated with a reduction in basophil allergen threshold sensitivity. Further studies are needed to show whether the changes in basophil sensitivity are of clinical relevance in pollen immunotherapy.

Complement factor C5a in acute exacerbation of Chronic Obstructive Pulmonary Disease.

The complement component C5a is a potent inflammatory peptide, which may be involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We analysed the induced sputum and plasma of 28 patients with stable COPD, 12 healthy smokers and 7 non-smokers. In 13 of the patients with COPD, we also observed paired samples during acute exacerbation. The concentrations of C5a/C5a desArg and C3a/C3a desArg were measured using cytometric bead array. Both C5a and C3a concentrations in induced sputum of stable patients with COPD were significantly increased compared to the control groups of healthy smokers and non-smokers. In addition, there was a significant elevation in C5a values in exacerbation of COPD that was independent from the airway C3a levels. Airway C5a levels were negatively correlated with forced expiratory volume in first second (FEV1)% predicted and diffusing capacity of the lung (TLCO). Plasma C5a concentrations in patients with COPD were significantly higher than in healthy smokers, but no further significant systemic C5a elevation was detected with acute exacerbation of COPD. There was no important difference in local or systemic C5a concentrations between healthy smokers and non-smokers. These in vivo results clearly show that local and systemic C5a concentrations in COPD are elevated, and that the local, in contrast to systemic, C5a concentrations additionally increase in the acute exacerbation of COPD. It seems that the cigarette smoke is not related to C5a increase. The elevated local and systemic C5a levels, and additional individual local C5a increase during the exacerbation support the importance of C5a in COPD.