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.

Recurrent COVID-19 Polymerase Chain Reaction (PCR) Positivity in 2 Patients During the Current Health Care System Crisis.

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic is becoming challenging for public health crisis management. Effective detection method such as the criterion standard real-time reverse-transcription polymerase chain reaction (rRT-PCR) test is the only reliable option for the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). RT-PCR detects the genetic material of the virus but does not distinguish the infectious periods. Other diagnostic methods as serological tests and computed tomography (CT) are less accurate but can provide complementary information, especially in the face of new SARS-CoV-2 variants. Here, we report 2 cases of coronavirus-infected patients with recurrent RT-PCR positivity after recovery, which raised questions about possible reinfection. CASE REPORT A married couple, a 44-year-old woman and a 45-year-old man, after COVID-19 recovery, from April to August 2020 presented dynamic RT-PCR outcomes (oscillating from negative to positive). Anti-SARS-CoV-2 immunoglobulin G (IgG) levels for both patients were 1000 U/ml, indicating seroconversion. As a result of recurrent positivity, the patients were isolated and had limited access to healthcare. In the follow-up period, combining RT-PCR results with serology testing and CT allowed determination of the patients' infectiousness. CONCLUSIONS Due to emerging coronavirus variants, individuals with dynamic PCR results, especially with post-COVID-19 syndrome, are indistinguishable from those who are infectious. Misdiagnosis causes unnecessary quarantines and exacerbates the health care crisis. Patients who had dynamic RT-PCR for SARS-CoV-2 require different diagnostics methods from those used in patients with a first-time positive test result. Combining diagnostic methods and identification of new variants of SARS-CoV-2 allows better estimation of the risk of reinfection.

Investigation of Repeatability of Peak Nasal Inspiratory Flow Rate Measurements Under Baseline Conditions and After Administration of 0.05% Oxymetazoline.

OBJECTIVES: Peak nasal inspiratory flow (PNIF) measurement is an inexpensive and user-friendly method to assess nasal patency. However, the repeatability of PNIF measurements, as well as the threshold value of a change in PNIF, which can be considered significant remain unclear. This study aims to investigate the repeatability of PNIF measurements and the change in PNIF after the administration of 0.05% oxymetazoline. METHODS: Repeated measurements of PNIF (Clement Clarke In-Check nasal inspiratory flow meter; Clement Clarke International, Ltd, Harlow, Essex, UK) were obtained in 333 healthy volunteers (174 women). Based on age, participants were categorized into three groups (6-7 years, 13-14 years, and 20-45 years). We obtained five measurements in each participant. PNIF was remeasured in 294 subjects 30 min after administration of 0.05% oxymetazoline. The variability in PNIF measurements was assessed using the coefficient of variation (CV = standard deviation × 100%/mean). RESULTS: The first four PNIF measurements significantly differed from each other. The difference in PNIF measurements ceased to be statistically significant only between the fourth and fifth measurements (p = 0.19). PNIF repeatability was acceptable; the median CV was 15.5% (0-66), which did not significantly differ between age groups. The administration of 0.05% oxymetazoline led to a statistically significant increase in the PNIF value by 14.3% (-45, 157%) (p = 0.000000). CONCLUSIONS: 1. No statistically significant difference was observed in PNIF values only between the fourth and fifth measurements; therefore, at least three measurements are essential to draw meaningful conclusions. 2. PNIF measurements were satisfactorily characterized by a relatively low CV (15%). 3. The administration of 0.05% oxymetazoline led to an increase in PNIF by approximately 14% over the baseline value.

Safety of bronchodilator reversibility test in elderly subjects: a prospective study.

INTRODUCTION: The reversibility test measures an increase in ventilation parameters after the administration of 400 mg of a short-acting ß-agonist (SABA). It is worth noting that a typical dosage, applied as a rescue medicine for bronchospastic dyspnoea, is significantly less, i.e., 100-200 mg. AIM: To assess the effects of inhaled 400 mg fenoterol (in the bronchodilator reversibility test) on the heart rate and the development of tachyarrhythmias in subjects aged 65 and above. MATERIAL AND METHODS: A total of 53 subjects (45 women) aged 77; 68-82 (median; interquartile range) in stable clinical condition were included in the study. Data including medical history, physical examinations, blood biochemistry, chest X-ray, 12-lead electrocardiogram, 24-hour Holter ECG monitoring, bronchodilator test, and echocardiography were obtained. During the Holter ECG monitoring, the bronchodilator test using 400 mg fenoterol (Berotec pMDI) was performed. RESULTS: A slight but statistically significant (p = 0.02) increase in heart rate from 71 to 75 per min (median) was noted after the administration of fenoterol. No statistically significant differences were found in the number of extrasystolic beats of either supraventricular (p = 0.42) or ventricular origin (p = 0.50). In addition, the subjects did not show any potentially dangerous arrhythmias or significant signs of coronary artery disease. However, there was a significant increase in the number of supraventricular beats in the subjects who were not taking ß-blockers. CONCLUSIONS: The use of 400 mg fenoterol in a bronchodilator reversibility test in elderly subjects does not entail any significant cardiovascular risk.

Studying allergic inflammation and spirometry over menstrual cycles in well-controlled asthmatic women: Changes in progesterone and estradiol affect neither FENO levels nor lung function.

It has been reported that female sex hormones influence on allergic inflammation and ventilation parameters in asthma but conclusions drawn by different researchers are divergent. The aim of our study was to assess the impact of progesterone (Pg) and estradiol (E) on the dynamics of allergic inflammation and spirometry test results in regularly menstruating women with stable allergic asthma. 13 women (28 days menstrual cycle), aged 18-45, taking no hormonal contraceptives, with mild and moderate asthma, without reported exacerbations at the near-ovulation and/or menstruation time, were monitored during two consecutive menstrual cycles. They had 4 visits per cycle (the first day of menstruation was assumed to be day 1 of the cycle; visits were carried out on days: 3-4, 10-11, 13-14 and 23-24). At each visit asthma symptoms, asthma control test (ACT) results, asthma treatment, fractioned nitric oxide (FENO) levels, spirometry test results, Pg and E, levels were analyzed. As a result of the study, no essential variability in FENO values and ventilation parameters' values in the course of menstruation cycle were observed. Negative correlation between FENO values and Pg concentrations was demonstrated (r = 0.27), but no correlation between FENO values and E levels was shown. No relationship between the ACT values and ventilation parameters and the levels of the sex hormones under investigation was detected. We conclude that changing levels of estradiol and progesterone (regardless of the negative correlation of progesterone and FENO values) affect neither the dynamics of allergic inflammation nor pulmonary function in women with stable allergic mild/moderate asthma.

The Impact of Sex and Age on the Prevalence of Clinically Relevant Sensitization and Asymptomatic Sensitization in the General Population.

The objective of our study was to evaluate the impact of sex and age on the prevalence of sensitization to inhalant allergens. The study was performed as a part of Polish Epidemiology of Allergic Diseases study, and data concerning citizens of Wroclaw were analyzed. The participants were divided into three age groups (6-7, 13-14, and 20-44 years) with a subdivision according to sex. We randomly selected 1409 individuals, 439 people complied; the complete set of tests was performed on 421 of them. We found that 37.7 % of the study population demonstrated sensitization to at least one of the allergens tested. Positive skin tests were found more frequently in males than in females (p = 0.003); among 6-7-year-old children, the sensitization was independent of sex (p = 0.26), while in two other groups, it was higher in males (p = 0.002 and p = 0.03, respectively). Clinically asymptomatic sensitization (AS) was found more often in females than in males (p = 0.04). The higher rate of AS in women was observed only in the two younger age groups, while in the 20-44-year-old group AS did not differ between the sexes (p = 0.72). Female sex hormones may contribute to a later change in the nature of sensitization from clinically asymptomatic to symptomatic. Further studies are needed to confirm the results of our study.

Sex-related clinical aspects in insect venom anaphylaxis.

Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable.

9α,11ß-PGF2, a Prostaglandin D2 Metabolite, as a Marker of Mast Cell Activation in Bee Venom-Allergic Patients.

Mast cell (MC) mediators, among them prostaglandin D2 (PGD2) and 9α,11ß-PGF2, PGD2's metabolite, play a key role in allergic reactions, including bee venom anaphylaxis (BVA). Assessment of these mediators has never been performed in BVA. The aim of the study was to assess the activation of MC during in vivo provocation with bee venom (BV) and to measure PGD2 and 9α,11ß-PGF2 in the course of an allergen challenge. The second aim was to determine if assessment of these mediators could be useful for predicting adverse events during venom immunotherapy (VIT). In 16 BV-VIT patients and 12 healthy subjects, levels of PGD2 and 9α,11ß-PGF2 were assessed during BV provocation by means of the skin chamber method. Chamber fluids, collected at 5 and 15 min, were analyzed for both mediators by gas chromatography mass spectrometry negative ion chemical ionization. BVA in comparison to non-allergic patients had a significantly higher ratio of 9α,11ß-PGF2 in allergen-challenged chambers to 9α,11ß-PGF2 in allergen-free chambers after 15 min of provocation (p = 0.039). Allergen challenge resulted in a significant increase of 9α,11ß-PGF2 levels between 5 and 15 min after provocation only in BVA patients (p < 0.05). Analysis of log-transformed PGD2 levels showed significant difference between changes in PGD2 concentration between BVA and healthy subjects. No study patient developed adverse reactions during. 9α,11ß-PGF2 is actively generated during the early allergic response to BV. Skin chamber seems to be a promising, non-invasive and safe model of in vivo allergen provocation in BV-allergic patients. High or low levels of both mediators do not predict occurrence of adverse events during VIT.

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.

[An attempt to estimate potentially useful parameters to evaluate the normal range of nasal peak inspiratory flow]. / Próba oceny parametrów przydatnych do wyznaczenia normy dla nosowego szczytowego przeplywu wdechowego.

INTRODUCTION: Measurement of peak nasal inspiratory flow (PNIF, peak nasal inspiratory flow) seems to be a cheap and simple method to assess nasal patency. Unfortunately, due to the lack of reference values a single measurement does not take any information about the degree of nasal obstruction. Therefore, the purpose of this study was to establish parameters useful for estimating PNIF reference values. MATERIAL AND METHODS: 221 respondents, from Wroclaw, answered a questionnaire based on ECRHS II and ISAAC. Sample was randomized based on the personal number, stratified and representative of age and sex. Subjects were divided into three groups on the basis of their age (6-7, 13-14 and 20-45 years). The PNIF was measured using an In-Check portable nasal inspiratory flow meter (In-Check's Clement-Clark). The highest of the five PNIF values was used as the measure of PNIF for each subject in subsequent analyses (PNIF MAX). Patients with rhinitis and/or asthma were withdrawn from the study. RESULTS: Repeated measurements of PNIF were performed in 221 healthy volunteers. PNIF values were higher in males compared to women and this difference was statistically significant. There was a statistically significant correlation between height and PNIF MAX, and there was no such correlation between age and PNIF MAX. Stepwise linear regression that included gender, height, age revealed that only sex and height were independent significant predictors of PNIF. Obtained dependence PNIF MAX = -137.7 - 22.5 x + 1.7 y, where x is the sex (a woman, 0 - male) and the y - height. Coefficient of determination (R(2)) was 0.45 which means that regression equation explains about 45% of the observed PNIF MAX variability. CONCLUSIONS: A correlation was found between PNIF value and sex and height of the patients, while age is irrelevant in this regard. Difficulty of establishing standards for the PNIF parameter are probably due to anatomical differences in the construction of the nose.

[Exhaled nitric oxide in patients with esophagitis]. / Stezenie tlenku azotu w wydychanym powietrzuu chorych na zapalenie przelyku.

INTRODUCTION: Assessment of nitric oxide (NO) concentration in exhaled air is broadly used to monitor the airway inflammation in asthma. High level of NO are also observed in paranasal sinuses and gastrointestinal tract (GT). The intact esopahageal sphincters are responsible for maintain the NO within the GT. It is not known how much the GT and especially esophageal motility disorders can affect the FeNO measurements. The aim of the study was to assess if the gastroesophageal reflux disease has any impact on level of NO in exhaled air in patients who do not suffer from any airway disease. MATERIAL AND METHODS: In 51 patients, in whom asthma, nasal polyps or atopy were excluded, gastroscopy with biopsy was performed. In 13 of them no esophageal pathology was found and they were considered as the control group. In the other 38 patients the esophagitis was diagnosed based on Los Angeles classification. RESULTS: The concentration of NO in exhaled air in patients with endoscopical gastro-esophageal changes did not differ significantly from the NO concentration in patients without inflammatory changes in stomach and esophagus (p = 0.68). Moreover, the presence of hiatal hernia did not affect the FeNO (p = 0.67). There was also no significant dependence between NO level and infection with Helicobacter pylori (p = 0.18). CONCLUSIONS: The gastroesophageal pathologies did not significantly affect NO concentration in exhaled air.

The G/G genotype of transforming growth factor beta 1 (TGF-beta1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

[Pathogenesis and clinical features of nonasthmatic eosinophilic bronchitis]. / Patogeneza i klinika nieastmatycznego eozynofilowego zapalenia oskrzeli.

The introduction of induced sputum, as the diagnostic and research tool allowed to define nonasthmatic eosinophilic bronchitis characterized as a chronic cough in patients with no symptoms or objective evidence of variable airflow obstruction, with normal airway hyperresponsiveness and sputum eosinophilia. Eosinophilic bronchitis is an important cause of chronic cough. Studies in which the assessment of airway inflammation has been undertaken in chronic cough patients have shown that nonasthmatic eosinophilic bronchitis accounts for 10 to 30% of cases referred for specialist investigation. Eosinophilic bronchitis, like asthma, is characterized by eosinophilic airway inflammation, but unlike asthma, there is no airway hyperresponsiveness or bronchoconstriction. The airway immunopathology of asthma and eosinophilic bronchitis are almost identical. An obvious question is why an apparently similar pattern of airway inflammation is associated with different functional abnormalities in patients with nonasthmatic eosinophilic bronchitis and asthma. The differences in functional association may be related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis.