Pre-seasonal immunotherapy is effective in both monosensitized and polysensitized patients with allergic rhinitis.

Summary: Background. The effectiveness of pre-seasonal allergoid immunotherapy in polysensitized patients are not well-known. The aim of the present study was to compare the clinical efficacy and immunological changes of pre-seasonal allergoid immunotherapy in mono and polysensitized patients with grass pollen allergy. Methods. Fourty six patients with seasonal allergic rhinitis undergoing pre-seasonal grass pollen immunotherapy and 28 cases followed by conventional drug treatment were included. These groups were divided into monosensitized and polysensitized ones. All patients were followed between March-September with symptom-medication scores, and visual analogue scale (VAS). The quality of life was assessed using the Mini-RQLQ questionnaire. Phleum pratense (Phl p) specific IgE and IgG4 (UNI-CAP 100, Phadia) measurements were performed before and after 7 weeks of immunotherapy. Results. In the immunotherapy group, 15th weekly symptom-medication scores and VAS scores between May and August were found to be significantly lower than those in the control group (p < 0.05). Phl p specific IgE and IgG4 levels were significantly higher after immunotherapy compared to those before immunotherapy (p = 0.001). Furthermore, Phl p specific IgG4 levels after immunotherapy were also significantly higher than in the control group (p = 0.001). Improvements in activities-practical problems and non-nose/eye symptoms quality of life scores were significantly different between two groups (p < 0.05). There was no difference in terms of clinical and immunological parameters in mono- and polysensitized patients (p > 0.05). Conclusions. This study indicates that clinical improvement with pre-seasonal grass pollen immunotherapy is accompanied by important increase in specific IgG4 blocking antibodies. Furthermore, a single-allergen immunotherapy can lead to similar clinical efficacy and immunological changes in polysensitized as well as monosensitized patients with grass pollen allergy.

Can dose reduction be made in patients with allergic bronchopulmonary aspergillosis receiving high-dose omalizumab treatment?

Summary: Objective. To reduce the omalizumab dose in patients with allergic bronchopulmonary aspergillosis (ABPA) who were on long-term omalizumab treatment. Methods. Once asthma was controlled, two approaches were used to reduce total monthly omalizumab dose, 1) both extending dose intervals from 2 to 4 weeks and decrease omalizumab dose, 2) to reduce omalizumab dose while keeping dose intervals stable. Results. Thirteen patients with ABPA (8F/5M, mean age 53.4 ± 13.0 years) were included. Pre-omalizumab, mean blood eosinophil count was 723.1 ± 547.1 cells/mcL, mean numbers of attacks and hospitalizations were 2.5 ± 1.5 and 1.3 ± 0.8, respectively. Median total monthly omalizumab dose was 750 (min 300, max 900) mg. First and 2nd approach to reduce omalizumab dose was used in nine and four patients with a median time of reduction 32 (min 13, max 47) months. The 2nd dose reduction was made in four patients at median of 23.5 months. Pre-omalizumab, mean oral corticosteroid (OCS, as methylprednisolone) dose was 12.2 ± 10.4 mg daily, it decreased to 0.69 ± 0.95 mg (p = 0.001) in the 1st year of omalizumab and could be stopped in 11 patients. Attacks and hospitalizations decreased to 0.31 ± 0.86 (p less than 0.001) and 0 (p = 0.003), respectively, in the 1st year of omalizumab. Total omalizumab dose was reduced by median 40% (min 20, max 60) in 1st intervention and 50% (min 20, max 67) after 2nd intervention. After omalizumab reduction, asthma control did not deteriorate and there was no need to increase the omalizumab or OCS-dose. Conclusions. Decreasing the total omalizumab dose does not cause clinical deterioration in ABPA after the disease is controlled.

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.

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.

T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns.

BACKGROUND: Secreted phospholipases A2 (sPLA2) represent antigens to which humans may be rarely or frequently exposed. Thus, the investigation of humoral and cellular immune responses to sPLA2s from different species can provide a suitable model in the study of antibody and T-cell cross-reactivity. METHODS: Specific IgE, IgG1, IgG4, and IgA antibodies were analyzed by ELISA against sPLA2s from pancreas of Bos taurus (BT), Apis mellifera (AM) bee venom, Daboia russellii (DR) and Naja mossambica (NM) snake venoms, and human group III (hGIII) sPLA2 using sera of nonallergic beekeepers, AM-allergic patients, and healthy controls. T-cell cross-reactivity was investigated in PBMC, and T-cell clones (TCC) are generated against AM sPLA2. RESULTS: Hyperimmune and allergic individuals showed high levels of sPLA2-specific IgG4 and significant IgG4 cross-reactivity between BT, DR, and NM sPLA2s. Furthermore, IgE, IgA, and IgG1 cross-reactivities against BT, DR, and NM sPLA2s were also detectable in the range of 22.2-44.8%. Allergic patients showed significant T-cell proliferative response to NM sPLA2 together with increased IFN-γ and IL-13 production even though they had never been exposed to cobra venom. Although nonallergic healthy controls show no cross-reactivity at T-cell level, they did have low levels of IgG4 and IgA against BT, DR, and NM sPLA2s. Human TCC spanning three major T-cell epitopes of AM sPLA2 showed minor proliferative response to NM and hGIII sPLA2s. CONCLUSIONS: This study shows that T cells and antibodies may show cross-reactivity between different species without being naturally exposed to sPLA2s.

Rush hymenoptera venom immunotherapy is efficacious and safe.

BACKGROUND: Although rapid venom immunotherapy (VIT) protocols have been shown to be safe and effective, this issue has not yet been clarified in Turkey. OBJECTIVE: The aim of this study was to evaluate the side effects of rush VIT as well as early clinical and immunological responses in patients with a venom allergy. METHODS: Eighteen patients who had a history of severe systemic reactions after Hymenoptera sting were included in the study. The diagnosis was made on the basis of positive skin test reactivity and the presence of specific IgE in serum to either bee or vespid venoms. Fourteen patients underwent an average 7-day rush VIT regimen under careful monitoring in our clinic. Among them 7 patients were treated with Vespula species and 7 with Apis mellifera venom extracts. Four patients were followed up as a control group. Skin test response, specific IgE and IgG4 levels were determined before and after a year of VIT. Local and systemic reactions due to injections were monitored during the induction and maintenance phases of VIT. RESULTS: Specific IgG4 levels significantly increased after 1 year compared with levels before VIT (mean concentration before and after; 13.04 vs 21.85 mg/L, respectively; P < .05) whereas specific IgE levels did not change (11.54 vs. 13.32 kU/L). No significant differences were observed before and after one year of VIT in skin prick (2.34 vs 3.66 mm) and intradermal (0.12-0.11 microg/mL) test reactivities (P > .05). A single patient treated with bee venom developed 4 mild systemic reactions (4/469 injections, 0.85%) during the course of VIT. More local reactions occurred in patients receiving bee venom extract (3.33%) than in those receiving yellow jacket venom (1.33%). Two patients tolerated field stings without reactions. CONCLUSION: Our experience confirms that rush VIT is safe and has a low systemic reaction. It can be considered for patients requiring rapid protection.

Differences between asthma and COPD in the elderly.

Asthma and chronic obstructive pulmonary disease (COPD) are both characterized by the presence of airflow obstruction. Both diseases are not rare in the elderly population. Distinguishing between these diseases is difficult and may be impossible in some older patients. The aim of the study was to investigate clinical and functional characteristics and the presence of atopic status in elderly subjects compared to COPD patients. Fifty-one patients over 60 years of age were selected for the study (27 patients with late-onset asthma, 24 patients with COPD). Atopy was defined by skin prick test and serum total IgE concentrations which were measured in all patients. Pulmonary function tests including airflow rates, lung volumes, airway resistance, diffusing capacity, and arterial blood gases analysis were performed in all patients. The rate of skin prick test positivity in asthmatics was significantly higher than that of the COPD patients. FEV1 was lower in COPD patients than in asthmatic patients. Bronchial reversibility in asthmatics became significantly higher than in COPD patients. While FRC and RV were increased in both groups showing same degree of pulmonary hyperinflation, patients with COPD demonstrated significantly decreased DLCO when compared to asthmatic patients. The level of both PO2 and PCO2 in patients with COPD significantly differed from asthmatics. In conclusion, a history of heavy smoking, decreased diffusing capacity for carbon monoxide, the presence of more prominent lung hyperinflation and chronic hypoxemia favour the diagnosis of COPD, whereas atopy and significant bronchodilator responsiveness favour the diagnosis of asthma.

The safety of allergen immunotherapy (IT) in Turkey.

Allergen immunotherapy (IT) has encouraging therapeutic outcomes but its safety is still being questioned because of possible severe systemic reactions. The aim of this study was to determine the frequency of systemic reactions (SR), and to identify their correlation with the characteristics of therapy, such as allergen composition and IT schedule, and diagnosis. We analyzed the data of 126 patients who received IT between 2000-2003, and suffered from respiratory allergy or hymenoptera venom anaphylaxis. IT was given by rush, clustered or conventional schedules. The standardized allergen extracts used were grass pollen, house dust mite and hymenoptera venom in 88, 18 and 20 patients, respectively. None of the patients received premedication. A total 4705 injections were administered. One hundred and twenty-three adverse events (AE) (2.6% per injection) were documented in 46 patients. Sixty-one of them were SRs (1.3% SRs per injection) and they were seen in 28 patients. Asthmatics had more tendency to SRs (p=0.05). Rush (1.8%) and clustered (2.8%) IT protocols were associated with a higher rate of SRs (per injection) when compared to conventional schedule (0.9%) (rush vs conventional; p=0.013, clustered vs conventional; p=0.001). The majority of SRs corresponded to grade 3 (49%). Forty-nine (80%) of the 61 SRs were observed during the build-up phase, and mostly with pollen extracts (75.5%). Patients showed more severe SRs during the build-up phase (p<0.05). Twenty-six (42.6%) of the SRs were immediate, whereas 35 (57.4%) SRs appeared within 2 hours. Delayed SRs were significantly more frequent in polysensitized patients when compared to monosensitized subjects (p=0.018). Our data indicate that rapid IT regimens and the presence of asthma represent a greater risk for SR development. Since the late SRs occur as frequently as the early ones, we suggest a longer waiting period beyond 30 minutes, especially in polysensitized and asthmatic patients.

Airway inflammation in nasal polyposis: immunopathological aspects of relation to asthma.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disorder of the upper respiratory tract, which is often coexist with asthma. However, the pathogenesis of especially in patients with NP is still a matter of debate. OBJECTIVE: To better understand the immunopathologic mechanism involved in this relationship, we investigated the inflammatory cell profiles in bronchial and nasal tissues of patients with NP alone and with concomitant asthma. METHODS: Seventeen patients with NP (six male, 11 female, age range: 19-63, mean age: 38.29+/-13.27 years) were selected for the study. Subjects were divided into two groups based on the presence of asthma or bronchial hyper-responsiveness (BHR). NP without BHR (Group 1) (n=8), NP and asthma or BHR (Group 2) (n=9). All patients underwent atopy evaluation including detailed history, skin prick test (SPT), total and specific IgE determination in sera. None of the subjects had taken inhaled, nasal or oral corticosteroids for at least 1 month before the study. Respiratory symptoms of asthmatic patients were controlled with only short acting beta(2)-agonist inhaler drugs as needed. NP tissue, nasal and bronchial mucosa biopsies were taken from all patients using fiberoptic endoscopy. CD3, CD8, CD16, CD68, AA1 (mast cell tryptase), human leucocyte antigen-DR (HLA-DR) and eosinophil peroxidase (EPO) expressing cells in specimens were determined by immunohistochemical methods. Positively staining inflammatory cell types were counted. Subepithelial lamina propria and periglandular areas were separately evaluated. RESULTS: No significant difference was found in polyp tissue, nasal and bronchial CD3(+), CD8(+), CD16(+), CD68(+), AA1(+), HLA-DR(+) and EPO(+) positive cells between groups. There were significantly higher numbers of CD8(+), CD16(+), HLA-DR(+), EPO(+) cells in the polyp tissue and nasal mucosa vs. the bronchial mucosa in all groups (P<0.05). However, CD8(+) cells were significantly increased in the polyp tissue and bronchial mucosa of patients with NP alone when compared with the patients with both asthma and NP (P<0.05). CD3(+), CD68(+) and CD16(+) cell counts were tended to be higher within the nasal polyp tissue of patients with isolated NP compared with counts within nasal and bronchial mucosa of patients with NP and asthma. Also, patients with isolated NP showed more HLA-DR(+) cells in the nasal polyp tissue and nasal mucosa than those of patients with NP and asthma. Immunoreactivity for EPO(+) eosinophils within the nasal and bronchial mucosa was more prominent in patients with NP and asthma compared with patients with NP alone. The number of EPO(+) eosinophils within the polyp tissue, nasal and bronchial mucosa was higher in the skin prick test negative (SPT -ve) group than the SPT positive (SPT +ve) ones. CONCLUSIONS: Our results demonstrate that infiltration of inflammatory cells in the nasal and the lower airways do not remarkably differ between patients with NP alone who has no evidence of BHR and asthmatic patients with NP. However, patients with SPT-ve NP reveal more intense eosinophilic inflammation in the entire respiratory mucosa.

The antioxidative defense in asthma.

Asthma is a disease characterized by chronic airway inflammation. Generation of oxygen free radicals by activated inflammatory cells produces many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. However, the activities of antioxidant enzymes and their relation with asthma have not been well defined. This study was performed to examine the activities of major intracellular antioxidants in mild asthmatic patients. Twelve asymptomatic mild asthmatic patients who never used any antiasthma medication and 13 age- and sex-matched healthy control subjects were selected. The activities of erythrocyte antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-Px) were measured spectrophotometrically. The mean SOD activity of asthmatic patients was found to be significantly lower than that of the controls (p < 0.05). There was no significant difference in CAT and GSH-Px activities between patients and controls (p > 0.05). Although the mechanisms underlying the association between asthma and antioxidant system are unclear, according to our findings, decreased antioxidant protection may contribute to the pathogenesis of mild asthma.

Is it important to perform pollen skin prick tests in the season?

BACKGROUND: Seasonal exposure to pollens causes the characteristic symptoms of respiratory allergy as well as an increase in specific IgE levels and inflammatory mediator release. However, little is known about the effect of natural allergen exposure on the skin test reactivity of patients with seasonal allergy. OBJECTIVE: The aim of this study was to investigate the monthly variation in skin test reactions with pollen allergens during pollen season and its relation to pollen counts. METHODS: Fifteen subjects with seasonal allergic rhinitis and/or asthma (4 male, 11 female) between the ages of 13 and 52 (mean 33.9 +/- 2.9) who lived in Ankara, Turkey were selected for this study. Patients were monitored from the beginning of March to the end of September 1997, and skin prick tests were performed using 5 grass, 12 tree, and 5 weed pollen allergen extracts every month. Atmospheric pollen grains were counted in the Ankara area between January and December, 1997. RESULTS: There were small but statistically significant increases in tree pollen-induced wheal sizes in May when compared with other months (P < 0.05). Skin test reactivity was correlated with tree pollen counts (r = 0.978, P < 0.05). There was not a significant difference in skin test reactivity to grass and weed pollens between months. CONCLUSIONS: Although skin test reactivity may be slightly greater to tree pollen during the tree pollen season, the timing of skin testing is not a critical determinant in patients with pollen allergy.

Atopic status of an adult population with active and inactive tuberculosis.

The rise in allergic disorders over the past three decades has been suggested to be related to the decrease in infectious diseases. Recently, a negative association between tuberculin responses and atopic disorders has also been reported. We planned to investigate the effect of natural exposure to Mycobacterium tuberculosis on atopic status in patients with active tuberculosis and to compare the findings with the data of patients with inactive disease. A total of 97 subjects were divided into two groups. Group 1, patients with proven active pulmonary tuberculosis (n = 66); group 2, subjects who had a history of previous tuberculous disease, with negative bacteriologic studies and no clinical and/or roentgenographic evidence of current disease (n = 31). Current history of allergic diseases was recorded by a physician with the use of a questionnaire adapted from the European Community Respiratory Health Survey (ECRHS), and skin-prick tests (SPTs) were performed using a standardized panel. Total IgE and Phadiatop were measured by the Pharmacia uniCAP system. The rate of one or more positive SPTs was significantly lower in the patients with active tuberculosis than the inactive group (15% versus 48.4%, p < 0.001). The current history of atopic diseases was 7.6% and 29% in the active and inactive tuberculosis groups, respectively (p = 0.002). The rate of positive skin tests to inhalant allergens in patients with inactive disease was higher than the rate of healthy adult Turkish people (48.4% versus 25%, p = 0.001). Geometric mean of total IgE levels were lower in patients with inactive disease than patients with active pulmonary tuberculosis (74.97 kU/L versus 106.3 kU/L, p = 0.05). The ratios of Phadiatop positivity were 21% and 38.7% in the active and inactive tuberculosis groups, respectively (p = 0.008). We found lower atopy rates in patients with active pulmonary tuberculosis than subjects with inactive disease. Although our data support the hypothesis that M. tuberculosis may prevent the development of atopic disorders by inducing the production of cytokines antagonistic to Th2 development, we believe prospective and experimental studies are needed before attributing a direct cause-effect link to this association.