Safety and Efficacy of VIT against Wasp Venom in Ultra-Rush Protocols in Patients Older Than 60 Years.

BACKGROUND: Allergen immunotherapy remains a widely recognized and widely used method for the treatment of selected allergic diseases. Currently, according to the European Academy Of Allergy and Clinical Immunology (EAACI) guidelines, venom immunotherapy (VIT) may be considered for patients over 60. Nevertheless, no separate studies have confirmed the efficacy and safety of this therapy. This study aimed to evaluate the short-term effectiveness of VIT against wasp allergens in an ultra-rush protocol for older patients compared to young patients. METHODS: Among the 113 patients included in this study, 51 were older than 60 years (Group A), and 62 formed the control "young group" (age range: 18-35 years). All patients were desensitized to wasp venom using the ultra-rush protocol according to Muller and aqueous solutions of vaccines containing wasp venom. A basophil activation test (Basotest, Orpegen Pharma, Germany) and intracutaneous tests with dilutions of wasp allergen and specific IgE to extract wasp venom were performed at the start and after six months of VIT. The safety of VIT was assessed on the basis of the international Mueller scale. RESULTS: One hundred and eleven patients with confirmed wasp allergies completed six months of VIT: 51 participants over 60 years of age (Group A) and 60 young people (Group B). No systemic adverse reactions were observed during the VIT induction phase. However, large local reactions were noted in 17% of older patients and 20% of young patients at a similar level (p > 0.05). During maintenance VIT, two mild grade I systemic reactions were confirmed in young patients. These symptoms resolved spontaneously. There were no such reactions in older patients. The effectiveness of VIT was tested using BAT. There was a statistically significant reduction in CD63 reactivity in 86% of patients in Group A, and a comparable and substantial decrease in 84% of young patients in Group B. According to the BAT test, the mean reductions in the area under the curve (AUC) after six months of VIT were significant (p < 0.05) and comparable between Groups A and B: -6.52 vs. 7.21. CONCLUSIONS: VIT against wasp venom is safe and effective in short-term observation, and is comparable to that used for young patients.

Elderly Patients and Insect Venom Allergy: Are the Clinical Pictures and Immunological Parameters of Venom Allergy Age-Dependent?

Insect venom is one of the most common triggers of anaphylaxis in the elderly population. Venom immunotherapy (VIT) remains the only treatment for Hymenoptera venom allergy (HVA). However, little is known about the differences in indication for VIT in the group of patients aged 60 years and older. The objective of this study was to assess the clinical and diagnostic differences of HVA in elderly patients. The study compared data from patients aged ≥ 60 (N = 132) to data from patients aged from 11 to 60 years (N = 750) in terms of HVA severity, comorbidities, and immunological parameters, namely, intradermal testing (IDT), specific IgE (sIgE) levels against extracts and major allergenic molecules, and serum tryptase level (sBT). The severity of systemic HVA (I-IV Müller scale) did not differ between adults and seniors. However, the severity of cardiovascular reactions (IV) increased with age, while the frequency of respiratory reactions (III) decreased. No differences were found in the immunological parameters of sensitization IDT, venom-specific IgE concentrations, or sIgE against Api m 1, 2, 4, 5, and 10 between patients below and above 60 or 65 years of age. Differences were noted for sIgE against Ves v1 and Ves v5; they were higher and lower, respectively, in seniors. In the seniors group, sBT levels were higher. Elevated tryptase levels, along with the aging process, can represent a risk factor within this age category. Nevertheless, advanced age does not influence the immunological parameters of immediate HVA reactions, nor does it impact the diagnosis of HVA.

Component-Resolved Evaluation of the Risk and Success of Immunotherapy in Bee Venom Allergic Patients.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment's inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR), (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller's scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV0) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I−III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom.

Clinical Characteristics and Management of Angioedema Attacks in Polish Adult Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency.

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is a rare disease characterized by recurrent swellings. This study aims to determine (i) the clinical characteristics of the HAE patient population from Poland, and (ii) real-life patients' treatment practices. A cross-sectional study involved 138 adult HAE patients (88 females, 50 males) treated in six regional HAE centers in Poland. Consecutive patients during routine follow-up visits underwent a structured medical interview on the clinical characteristics of the course and treatment of HAE attacks within the last six months. A total of 118 of 138 patients was symptomatic. They reported in total 2835 HAE attacks predominantly peripheral and abdominal, treated with plasma-derived C1-INH (61.4%), icatibant (36.7%) and recombinant C1-INH (1.9%). An amount of 116 patients carried the rescue medication with them while traveling, and 74 patients self-administrated on demand treatment. There were twice as many symptomatic women (n = 78) as there were men (n = 40). Women treated their HAE attacks significantly more often than men. Older patients (≥65 years) reported a longer delay in diagnosis, and practiced the self-administration of rescue medication less frequently in comparison to other patients. Clinical features of the surveyed population are similar to other European, but not Asian, HAE patient groups. Self-administration still remains an unmet medical need. Some distinct HAE patients may require special attention due to the severe course of the disease (females) or a delay in diagnosis (the elderly).

Pfizer-BioNTech COVID-19 Vaccine Tolerance in Allergic versus Non-Allergic Individuals.

Individuals with a history of allergy are potentially at risk of suffering from adverse effects after COVID-19 vaccination. We sought to assess the tolerance towards the Pfizer-BioNTech vaccine in allergic patients. To address this issue, we used a questionnaire conducted on-line in a group of medical professionals who were vaccinated with the Pfizer-BioNTech vaccine. A total of 1808 respondents, out of whom 1707 received two doses of the vaccine, returned the questionnaire. Local reactions after injection were more frequent in allergic individuals after both doses (swelling p = 0.0003). Systemic adverse events (AE-SYS) occurred more often after the second than the first dose in both groups (allergic persons: 77.29% vs. 41.06%); vomiting and arthralgia occurred more often in allergic subjects (p = 0.0009). AE-SYS in allergic individuals lasted longer than in non-allergic ones after the first (p = 0.01) and the second dose (p = 0.0009). Allergic reactions after vaccination were reported more frequently in allergic subjects: after the first dose (p = 0.00001) and after the second dose (p = 0.001). Rhinitis was the most frequent symptom observed more often in allergic patients. No severe allergic reactions occurred during the full cycle of vaccination. Although the Pfizer-BioNTech vaccine is tolerated worse by allergic than non-allergic individuals, the occurring adverse symptoms are mild and do not preclude a successful completion of the vaccination cycle. The presence of symptoms suggestive of allergy does not constitute a condition of increased risk of developing clinically significant adverse events following Pfizer COVID-19 vaccination.

Simultaneous Influenza Vaccination and Hymenoptera Venom Immunotherapy Is Safe.

Allergen immunotherapy (AIT) is a standard treatment for venom allergy. Our purpose was to determine if the administration of both allergen and protective vaccines during one visit is safe and if such a procedure does not deteriorate the tolerance of both vaccines. As current guidelines are based on theoretical assumptions, our aim was to establish the safety and tolerance of shortening the recommended interval between vaccinations. During two influenza seasons, 44 adult patients, with a history of systemic allergic reactions after a Hymenoptera sting, underwent 58 simultaneous allergen and seasonal influenza vaccinations (study group) while in the maintenance phase of venom immunotherapy (VIT). The control group consisted of 57 healthy adults who were vaccinated against influenza only. The conditions of the patients were monitored during hospital visits, and via telecommunication methods to evaluate the safety and tolerance of the procedure. Within the study group, there were no immediate or delayed allergic reactions after vaccinations. The presence of common, adverse influenza vaccine reactions among study group patients (29%) and control group patients (32%) did not differ significantly (p = 0.841). We did not observe a difference in the frequency of various adverse reactions in either group or a dependence of previous vaccinations against influenza on the occurrence of adverse reactions. The most frequent occurrences were local adverse reactions. All adverse reactions were resolved without treatment. These findings demonstrate the safety and tolerance of an influenza vaccination and Hymenoptera venom immunotherapy administration during one visit.

Eradication of Helicobacter pylori, as add-on therapy, has a significant, but temporary influence on recovery in chronic idiopathic urticaria: a placebo-controlled, double blind trial in the Polish population.

INTRODUCTION: The infectious factor like Helicobacter pylori (HP) has been thought to trigger the vicious circle of chronic idiopathic urticaria (CIU), therefore its eradication could modify the course of the disease. AIM: To reveal the influence of HP eradication on CIU clinical course. MATERIAL AND METHODS: Sixty-four CIU patients, receiving fexofenadine, as the basic treatment, took part in the research, divided into 3 groups: HP patients treated by eradication, HP patients receiving placebo, and patients without bacteria. Gastroscopy, urease test and histopathology were done to detect HP. Patients with HP were randomized and received eradication treatment or placebo. The efficacy of eradication was checked after 6 weeks by means of another gastroscopy, urease test and histopathology. In the 6th week and in the 4th and 6th month after eradication, the symptoms were evaluated basing on the score symptom scale. RESULTS: Helicobacter pylori did not occur more frequently in CIU patients than in the healthy population. A statistically significant clinical improvement of CIU symptoms was observed in the 6th week after eradication as compared to the group receiving placebo (p = 0.02) and patients who were not infected (p = 0.02). Further observation in the eradicated patients group revealed the rebound phenomenon - worsening of the clinical state (p = 0.001), which in the 4th month did not differ from the patients not infected or patients receiving placebo. CONCLUSIONS: Although HP occurs as frequently in CIU patients as in the healthy population, eradication, added to basic antihistaminic treatment, has a significant influence on CIU patients' recovery parallel to the reduction of stomach inflammation features.

Autoreactive IgE in Chronic Spontaneous/Idiopathic Urticaria and Basophil/Mastocyte Priming Phenomenon, as a Feature of Autoimmune Nature of the Syndrome.

Recent years of research have shed a new light on the role of IgE in immune reactions. It seems to be more than just a contribution to immediate type of allergic response. It appears that monomeric IgE may enhance mast cell activity without cross-linking of FcεRI by IgE specific allergen or autoreactive IgG anti-IgE antibodies. Monomeric IgE molecules are heterogeneous concerning their ability to induce survival and activation of mast cells only by binding the IgE to FcεRI, but not affecting degranulation of cells. It also turned out that IgE may react to autoantigens occurring in the blood not only in chronic spontaneous urticaria (CSU) but also in other autoimmune diseases. The aforementioned phenomena may promote the activity of mast cells/basophils in CSU that easily degranulate when influenced by various inner (autoreactive IgG against IgE and FcεRI, autoreactive IgE for self-antigens) and outer factors (cold, heat, pressure) or allergens. These findings forced the new approach to the role of autoimmunity, self-antigens and IgE autoantibodies in the pathology of CSU. CSU put in the scheme of autoreactive IgG and autoreactive IgE seems to be either a kind of an autoimmune disease or a clinical manifestation of some other defined autoimmune diseases or both.

Impact of Birth Weight and Smoking on Lung Function in Patients with Asthma, COPD, and Healthy Volunteers.

BACKGROUND: Birth weight (BW) is an important factor for determining the development of the respiratory system. The majority of research analyzed the impact of BW on lung function in youth. BW influence and smoking on lung function in adults with asthma and COPD is an interesting issue. OBJECTIVES: The aim of the study was to investigate relationships between BW, smoking, and lung function in adult healthy individuals and diagnosed with asthma or COPD. MATERIAL AND METHODS: Four hundred seventy-nine subjects were divided into 5 groups: 123 healthy non-smokers, 180 healthy smokers, 72 non-smoking asthmatics, 57 smoking asthmatics, and 47 COPD patients. Relationships between 4 BW quartiles and lung function was analyzed with respect to smoking. RESULTS: Impact analyzes of BW, smoking, and asthma on FVC% revealed that asthma is the only significant differentiating factor in this spirometric parameter (p < 0.01). FEV1% was significantly influenced by asthma and BW, and FEV1/ FVC% was exclusively influenced by asthma. Spirometric parameters increased proportionally to particular BW quartiles in healthy non-smokers group; however optimal BW quartile predicting increase of parameters was 2751-3250 g. In asthma, BW quartile predicting the increase of spirometric parameters was 3251-3750 g, but BW quartile predicting decrease of FEV1/FVC% was 2751-3250 g. The comparison of results between COPD group and results from other 4 groups showed that values of all parameters in patients with COPD did not change proportionally to all quartiles of BW. In terms of FEV1/FVC%, the proportional increase of parameter in BW quartile 2751-3250 g was observed. CONCLUSIONS: BW, as independent factor influences on spirometric parameters of healthy individuals, patients with asthma, COPD in a differentiated manner depending on quartile of BW rather than on simple linear increase of BW, regardless of smoking.

Occurrence of fibronectin-fibrin complexes in plasma of patients with multimorbidity due to the inflamm-aging phenomenon.

BACKGROUND: Multimorbidity is the co-occurrence of chronic diseases associated with low-grade chronic inflammation of connective tissue. AIM OF STUDY: Frequency of occurrence and relative amounts of fibronectin (FN) complexes with fibrin (FN-fibrin) and FN monomer were analyzed in 130 plasma samples of 18 to 94-year-old multimorbid patients in relation to concentrations of FN and extra domain A (EDA)-FN, and C-reactive protein (CRP) as well as to age, number of coexisting chronic diseases and presence of specified diseases. RESULTS: Immunoblotting revealed, besides FN dimer, the presence of FN monomer, and 750-, 1000-, and 1300-kDa FN-fibrin complexes in the multimorbid plasmas. The FN-fibrin complexes appeared more frequently and in higher relative amounts, but FN monomer less frequently and in a lower relative amount in the groups of elderly multimorbid patients, with a higher number of coexisting diseases and with dominance of cardiovascular diseases and osteoarthrosis, and with CRP concentration of 3-5mg/l. In contrast, the normal plasma contained only the FN-fibrin complex of 750 kDa in a lower relative amount, but with an increasing amount with normal aging. Moreover, FN concentration increased and EDA-FN decreased with the number of co-existing diseases and aging of patients, although both concentration values were lower than in the age-matched normal groups. FN concentration was the lowest in the exacerbation of a chronic disease and EDA-FN in the stable chronic disease groups. CONCLUSION: The alterations in plasma FN molecular status were associated with micro-inflammation and micro-coagulation, as well as multimorbidity of subjects and their physiological aging.

Fractioned exhaled nitric oxide (FE(NO)) is not a sufficiently reliable test for monitoring asthma in pregnancy.

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameter's considerable intrasubject variability, regardless of the degree of asthma control.

[The long-term variability of FeNO in pregnant asthmatic women with controlled asthma]. / Dlugoterminowa zmiennosc stezenia tlenku azotu w wydychanympowietrzu (FeNO) w astmie kontrolowanej u kobiet w ciazy.

INTRODUCTION: Fractional exhaled nitric oxide (FeNO) is considered as a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intra-subject variability of this parameter as well as the rate of its change, which can be clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. MATERIAL AND METHODS: Pregnant, non-smoking women with asthma were recruited between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and the asthma control test (ACT) was completed during monthly visits up to delivery. The data of 26 subjects with well-controlled asthma during pregnancy (ACT values within the range 20-25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation x 100%/arithmetic mean). RESULTS: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well-controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50ppb (39%; 11.8-121.9%) and those with all FeNO values below 50ppb (29.9%; 11.3-71.8%), as well as between atopic (35.7%; 11.8-121.9%) and nonatopic (24.2%; 11.3-71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). CONCLUSIONS: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well-controlled asthma indicates that changes in this parameter should be interpreted with caution while being used for asthma treatment monitoring.

[Birth weight as a factor determining lung function among healthy persons and its relation with chronic pulmonary disease]. / Urodzeniowa masa ciala jako czynnik determinujacy funkcje pluc osób zdrowych i jej zwiazek z przewleklymi schorzeniami ukladu oddechowego.

Low lung function is associated with increased risk of morbidity and mortality in the population. Lung development seems to be important factor in pathogenesis of respiratory disorders. Airway development is a complex process. Birth weight (BW) is one of perinatal factors which influences development of pulmonary system and multiorgan function of the body. Aforementioned relationships are visible especially at first years of life. However, not very many studies have examined the associations between birth weight and lung function in later age then childhood and adolescence. The aim of this review is to discuss relationships between BW and lung function parameters in healthy individuals and patients with lung disease in childhood and adulthood.

Serum concentration of C-reactive protein is not a good marker of bronchial hyperresponsiveness.

INTRODUCTION: Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated. MATERIALS AND METHODS: One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests. RESULTS: Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25-75% quartiles: 0.6-2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25-75% quartiles: 0.8-2.4 and median: 0.9 mg/l, 25-75% quartiles: 0.5-2.8, respectively; p=0.297). There was no statistically significant correlation (r = -0.163, p = 0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p = 0.22, CONCLUSIONS: Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.

[Pathogenic and clinical significance of Helicobacter pylori infection in chronic urticaria and angioedema]. / Znaczenie patogenetyczne i kliniczne zakazenia Helicobacter pylori w przewleklej pokrzywce i obrzeku naczynioruchowym.

Urticaria and angioedema are one of the most frequent skin diseases, nevertheless no etiologic factors have been found in a large number of cases. This review summarizes the available medical literature from Medline regarding Helicobacter pylori and mentioned disease. Different studies have shown a high prevalence of Helicobacter pylori infection in patients with chronic urticaria, and occasional remission of the skin lesions after eradication therapy. However there are several papers, which support lack of relationship between H. pylori infection and the course of urticaria and angioedema. Thus we need further randomized, double-blind and placebo controlled studies including adequate diagnostic schedules, sufficient eradication treatment protocols, confirmation of eradication, and adequate control groups to establish a role of H. pylori in urticaria and angioedema.