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Biomarkers that are able to predict the response to omalizumab (OMA) in chronic spontaneous urticaria (CSU) are highly valued. The aim of our study was to evaluate the UAS7 (urticaria activity score assessed for 7 days), DLQI (dermatology life quality index), SII (systemic immune-inflammation index), SIRI (systemic inflammation response index), PLR (platelet/lymphocyte ratio) and NLR (neutrophil/lymphocyte ratio) in a group of 46 CSU a patients treated for 24 weeks with OMA (300 mg every 4 weeks). There were no statistically significant differences observed at the start nor at the end of the treatment between the two groups (responders vs. non-responders) and SII, SIRI, PLR and NLR. However, a statistically significant correlation was observed between severity of urticaria expressed in UAS7 scores and the quality of life (evaluated by DLQI). Furthermore, at week 24, both groups demonstrated significant improvement in quality of life. Our single center study did not confirm the usefulness of SII, SIRI, NLR or PLR as predictors of the response to OMA in CSU. However, it is of importance that even patients who did not respond to the treatment presented a significant improvement in quality of life. Additionally, we also observed that the efficacy of treatment was unchanged amongst patients who underwent a second series of treatment in cases of relapse.

Cholinergic urticaria (CholU) is a chronic inducible urticaria, characterised by itchy pinpoint wheals up to 3 mm in diameter, surrounded by a prominent flare, that occur following an exposure to characteristic triggers such as active or passive heating, physical exercise, emotions, hot or spicy foods. Key pathophysiologic mechanisms include immediate hypersensitivity to autologous sweat antigens, functional sweating disorders, impaired acethylcholine metabolism, abnormal skin vascular permeability and disturbed skin innervation. Clinical manifestations of CholU may vary from typical itchy pinpoint urticarial lesions, angioedema to anaphylaxis. Atypical CholU forms include cholinergic pruritus, cholinergic dermographism, cold cholinergic urticaria and persistent cholinergic erythema. The diagnosis of cholinergic urticaria relies on patients history, сlinical manifestations and challenge tests. Treatment options include nonsedating H1 antihistamines in standard or increased doses. The evidence is accumulating for the use of biological treatment with omalizumab in cholinergic urticaria. The prospect of personalized treatment of cholinergic urticaria include autologous sweat desensitization. The main research efforts in ColdU are directed at optimizing diagnostic approaches and developing innovative therapeutic options.

This review presents state-of-the-art knowledge and identifies knowledge gaps for future research in the area of exercise-associated modifications of infection susceptibility. Regular moderate-intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. However, strenuous exercise, as performed by professional athletes, may promote infection: in about half of athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance the release of pro-inflammatory mediators, which may induce infection-like respiratory symptoms. Relatively few studies have assessed the influence of regularly repeated exercise on the immune response and systemic inflammation compared to the effects of acute exercise. Additionally, ambient and environmental conditions may modify the systemic inflammatory response and infection susceptibility, particularly in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms, resulting in decreased specific and non-specific response in competitive athletes. The most promising areas of further research in exercise immunology include detailed immunological characterization of infection-prone and infection-resistant athletes, examining the efficacy of nutritional and pharmaceutical interventions as countermeasures to infection symptoms, and determining the influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS-CoV-2. By establishing a uniform definition of an "elite athlete," it will be possible to make a comparable and straightforward interpretation of data from different studies and settings.

This review presents state-of-the-art knowledge and identifies knowledge gaps for future research in the area of exercise-associated modifications of infection susceptibility. Regular moderate-intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. Infection-promoting consequences are attributed to strenuous exercise as performed by professional athletes. In about half of the athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance release of proinflammatory mediators thus probably leading to appearance of infection-like respiratory symptoms. Studies assessing influence of regularly repeated exercise on immune response and systemic inflammation are far less numerous than those regarding acute exercise effects. This identifies another knowledge gap requiring further assessment both in recreational and in professional athletes Additionally, ambient and environmental conditions modify systemic inflammatory response and infection susceptibility in particular in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms resulting in decreased specific and non-specific response in competitive athletes. Most promising areas of further research in exercise immunology include: detailed immunological characterization of infection-prone and infection-resistant athletes; efficacy of nutritional and pharmaceutical interventions as countermeasures to infections’ symptoms; and influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS-CoV-2. Establishing uniform definition of “elite athlete’ shall hopefully allow for comparable and straightforward interpretation of data coming from different studies and settings.

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.

Purpose This paper aims to present the results of experimental and numerical research on heat transfer distribution under the impinging jets at various distances from the wall and high jet velocity. This work is a part of the INNOLOT Program financed by National Centre for Research and Development. Design/methodology/approach The air jets flow out from the common pipe and impinge on a surface which is cooled by them, and in this way, all together create a model of external cooling system of low-pressure gas turbine casing. Measurements were carried out for the arrangement of 26 in-line jets with orifice diameter of 0.9 mm. Heat transfer distribution was investigated for various Reynolds and Mach numbers. The cooled wall, made of transparent PMMA, was covered with a heater foil on which a layer of self-adhesive liquid crystal foil was placed. The jet-to-wall distance was set to h = from 4.5 to 6 d. Findings The influence of various Reynolds and Mach numbers on cooled flat plate and jet-to-wall distance in terms of heat transfer effectiveness is presented. Experimental results used for the computational fluid dynamics (CFD) model development, validation and comparison with numerical results are presented. Practical implications Impinging air jets is a commonly used technique to cool advanced turbines elements, as it produces large convection enhancing the local heat transfer, which is a critical issue in the development of aircraft engines. Originality/value The achieved results present experimental investigations carried out to study the heat transfer distribution between the orthogonally impinging jets from long round pipe and flat plate. Reynolds number based on the jet orifice exit conditions was varied between 2,500 and 4,000; meanwhile, for such Re, the flow velocity in jets was particularly very high, changing from M = 0.56 to M = 0.77. Such flow conditions combination, i.e. the low Reynolds number and very high flow velocity cannot be found in the existing literature.

Exercise-induced respiratory symptoms describe acute airway narrowing that occurs as a result of exercise. It includes exercise-induced bronchoconstriction (EIB) and exercise-induced asthma (EIA) issues. To provide clinicians with practical guidelines, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB/EIA and to develop evidence-based guidelines for the diagnosis and treatment. Recommendations for the diagnosis and treatment of EIB were developed. High-intensity exercise in polluted environment (cold air, humidity, contamination, allergens) may increase the risk of EIB and asthma symptoms in athletes. Diagnostic procedures should include history taking, physical examination, atopy assessment and functional tests of the respiratory system. A strong recommendation was made for regular use of inhaled glucocorticosteroids and avoidance of short-acting β2-agonists as the only treatment. The treatment of asthma in athletes should always take into account current anti-doping regulations. This position paper reflects the currently available evidence.

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming-pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since they have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of these volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming-pools (water ingestion, skin absorption and inhalation) contribute to the individual exposome. CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated-pools as customers, particularly children, may also be affected has been a matter of debate. In this article, the EAACI Joint Task Force of the Working Group of Allergy, Asthma & Sports and the Interest Groupf of Environmental & Occupational Allergy discusses the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports and recreational attendance) and identify the main recommendations and unmet needs for research in this area.

Publisher's version (útgefin grein), Background: The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods: A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results: A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). Interpretation: In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons., European Commission, Grant/Award Number: FOOD-CT-2005-514000 and FP7-KBBE-2012-6; grant agreement no. 312147

Intensive exercise modifies airway inflammation and infection susceptibility. We aimed to determine the effect of exercise on pro- and anti-inflammatory cytokine (TNF-α, IL-1ra, IL-10) and innate immunity protein (HSPA1, sCD14) levels in exhaled breath condensate (EBC) and nasal secretions of competitive athletes, non-exercising asthmatics and healthy controls (HC).The study group consisted of 15 competitive athletes (five speed skaters and ten swimmers) aged 15-25. The control groups comprised 10 mild-to-moderate asthmatics (AC) and seven HC. Athletes were assessed in- and off-training while asthmatics and controls at one time point. Nasal lavages and EBC were collected before and after a treadmill exercise challenge. Protein levels were assessed using ELISA.TNF-α levels in EBC were significantly higher in athletes than HC, but similar to asthmatic patients. In contrast, IL-1ra EBC concentrations were significantly lower in athletes than in HC, but again similar to asthmatics. Significant positive correlations were seen between baseline concentrations of TNF-α in EBC and fall in FEV1 following exercise challenge in athletes during training period (R=0.74, p0.01) and in asthmatics (R=0.64, p0.05). In nasal secretions, baseline IL-1ra levels were significantly higher in athletes and asthmatics than in HC. Exercise caused a slight, yet significant, increase in EBC HSPA1 in athletes (p=0.02). The exercise challenge did not considerably influence TNF-α, IL-1ra, HSPA1 and sCD14 in EBC or nasal secretions.Dysregulation of the TNF-α/IL-1ra balance in EBC and nasal secretions from athletes may reflect the presence of airway inflammation induced by repeated strenuous exercise.

INTRODUCTION Periostin is a matricellular protein expressed by many tissues. Its release may be enhanced, among others, through mechanical stimulation of muscles and bones as well as by cytokines of allergic inflammation. OBJECTIVES Our aim was to assess periostin levels in serum and exhaled breath condensate (EBC) of professional athletes, asthmatics and healthy controls. We also sought to determine whether acute treadmill exercise influences serum and EBC periostin. METHODS Study groups included 9 competitive swimmers, 10 mild-to-moderate asthmatics and 7 healthy controls. Athletes were assessed twice (in- and off-training period) while asthmatics and controls in one time-point. Data on demographics, allergy symptoms and exercise load were acquired through Allergy Questionnaire for Athletes (AQUA) and International Physical Activity Questionnaire (IPAQ). Serum and EBC were collected before and after treadmill exercise challenge. RESULTS Baseline serum periostin in swimmers during training period was significantly higher (5- to 7-fold) than in asthmatics (P = .01) and controls (P < .05). In EBC, lowest periostin levels were seen in athletes in-training as compared with off-training period (P < .01) and with asthmatics (P < .03). Acute bout of exercise did not induce significant changes neither in serum nor in EBC periostin in any group. CONCLUSION Increased serum, but not EBC, periostin levels in competitive athletes are probably because of permanently increased exercise load leading to stimulation, injury and regeneration of musculoskeletal tissues. Periostin may be considered marker of long-term exercise overload after confirmation in larger groups.

Introduction Regular training modulates airway inflammation and modifies susceptibility to respiratory infections. The impact of exercise and ambient conditions on airway hyperreactivity and innate immunity has not been well studied. We aimed to assess exercise-related symptoms, lung function, airway hyperresponsiveness and innate immunity proteins in relation to meteorological conditions and exercise load in competitive athletes. Material and methods Thirty-six speed skaters were assessed during winter (WTP) and summer (STP) periods. The control group comprised 22 non-exercising subjects. An allergy questionnaire for athletes (AQUA) and IPAQ (International Physical Activity Questionnaire) were used to assess symptoms and exercise. Meteorological parameters were acquired from World Meteorological Organization resources. Serum innate immunity proteins were measured by ELISA. Results Exercise-associated respiratory symptoms were reported by 79.4% of skaters. Despite similar exercise load and lung parameters during both periods, positive methacholine challenge was more frequent during winter (p = 0.04). Heat shock protein HSPA1 and IL-1RA were significantly decreased during STP compared to WTP and controls. During WTP, IL-1RA was elevated in skaters reporting exercise-induced symptoms (p = 0.007). sCD14 was elevated in athletes versus controls in both periods (p < 0.05). HSPA1 was significantly higher in WTP compared to STP irrespective of presence of respiratory tract infections (RTIs). IL-1RA in WTP was elevated versus STP (p = 0.004) only in RTI-negative athletes. Serum IL-1RA negatively correlated with most meteorological parameters during WTP. Conclusions Ambient training conditions, but not training load, influence bronchial hyperreactivity and the innate immune response in competitive athletes assessed during winter. The protective effect of regular exercise against respiratory infections is associated with a shift in serum innate immunity proteins.

Marek L. Kowalski was a dedicated scientist and clinician, dynamic leader and organizer, as well as committed educator and mentor for many students, researchers and doctors. His discoveries in human immunology, his empirical and implementation works made a significant contribution to modern medical knowledge and practice in the field of pathogenesis, diagnosis and treatment of allergic diseases, bronchial asthma, and hypersensitivity to non-steroidal anti-inflammatory drugs.

The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA ) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms is of major importance as EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby, we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads toward better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.

ispartof: ALLERGY vol:74 issue:11 pages:2244-2248 ispartof: location:Denmark status: published

Background Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. Aim To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Methods Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Results Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Conclusion Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Purpose Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. Methods Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. Results Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. Conclusions Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.

Purpose Respiratory viral infection and nonsteroidal anti-inflammatory drugs (NSAIDs) may affect arachidonic acid (AA) metabolism in the airway epithelium, however their joint effect has not been studied. We hypothesized, that alternations of AA metabolism in human airway epithelial cells (ECs) – induced by Parainfluenza virus type 3 (PIV3) – may be modified by concomitant treatment with NSAIDs. Materials and methods Nasal (RPMI 2650) and bronchial (BEAS-2B) epithelial cells were cultured into confluence and then infected with PIV3. Prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) levels in cell supernatants were measured by ELISA and expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) mRNA in cells was evaluated after reverse transcription with real-time polymerase chain reactions. Results PGE2 generation was decreased by PIV3 infection in the upper airway epithelial cells, and increased in the lower airway epithelial cells. Both naproxen and celecoxib induced significant reduction in PGE2 release in both infected and non-infected upper and lower airway epithelial cells. However, in PIV3-infected epithelial cells celecoxib inhibited PGE2 release and COX-2 expression to significantly higher degree as compared to non-infected cells. 15-HETE generation or COX-1, 5-LO and 15-LO expression were not affected by the virus infection or by NSAIDs. Conclusion Virus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation.

Background: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. Objective: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. Methods: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. Results: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-&beta, and RANTES mRNA expression was higher in injured ECs and IFN-&alpha, IFN-&beta, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-&alpha, and IFN-&beta, mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.

Experimental analyses of four own developed synthetic jet generator designs were presented in this paper. The main task of this work was to find the most appropriate design of the synthetic jet generator. Dynamic characteristics of the synthetic jet generator׳s diaphragm with piezoelectric material were measured using non-contact measuring equipment laser vibrometer Polytec ® PSV 400. Temperatures of the piezoelectric diaphragms working in resonance frequency were measured with Fiber Bragg Grating (FBG) sensor. Experimental analysis of the synthetic jet generator amplitude–frequency characteristics were performed using CTA (hot wire anemometer) measuring techniques. Piezoelectric diaphragm in diameter of 27 mm was excited by sinusoidal voltage signal and it was fixed tightly inside the chamber of the synthetic jet generator. The number of the synthetic jet generator orifices (1 or 3) and volume of cavity (height of cavity vary from 0.5 mm to 1.5 mm) were changed. The highest value of the synthetic jet velocity 25 m/s was obtained with synthetic jet generator which has cavity 0.5 mm and 1 orifice (resonance frequency of the piezoelectric diaphragm 2.8 kHz). It can be concluded that this type of the design is preferred in order to get the peak velocity of the synthetic jet.

This chapter presents the results of numerical investigations of a synthetic jet actuator for an active flow control system. The Moving–Deforming-Mesh (MDM) method as a boundary condition is used to capture the real physical phenomenon and investigate the influence of the membrane amplitude, the forcing frequency, and cavity effect on the jet velocity. Different cases are investigated to maximize the jet velocity—an actuator with one and two membranes in a cavity, with perpendicular and parallel membranes. Two main forcing frequencies can be specified in the synthetic jet actuator application. One corresponds to the diaphragm natural frequency, and the other corresponds to the cavity resonant frequency (the Helmholtz frequency). Results of actuators operating at the two abovementioned forcing frequencies are presented. The simulation results show an increase in the jet velocity as a result of an increase in the membrane peak-to-peak displacement. Synthetic jet actuators’ impact on the flow separation reduction will be investigated on the bump model. Preliminary simulation results of the flow separation over the bump are presented in this chapter as well.

Introduction Exercise-induced respiratory symptoms are often reported by professional athletes, but asthma and allergy are underdiagnosed. Few studies used standardized questionnaires combined with clinical assessment to investigate asthma and allergy among athletes. Objectives Assessment of the prevalence of allergy and asthma symptoms among Polish professional athletes and confronting it with clinical data. Methods Two hundred twenty-two Olympic athletes participated in the project being part of the Global Allergy and Asthma European Network (GA2LEN) Olympic study. Allergy and asthma status was determined using Allergy Questionnaire for Athletes (AQUA), spirometry, reversibility test, methacholine challenge and skin prick testing. Final diagnosis was established by an allergist. Results At least one exercise-induced asthma (EIA) symptom was reported by 28.4% athletes, and finally asthma diagnosis was established in 11.3% while only 5.9% of athletes had history of asthma. Reversibility test was positive in 36% of athletes finally diagnosed with asthma. Allergic rhinitis (AR) symptoms were reported by 27%, and the diagnosis was confirmed in 21% of athletes while only 9% had previously diagnosed AR. No significant differences in frequency of asthma and AR were observed between endurance and non-endurance athletes. Conclusions High prevalence of exercise-induced respiratory symptoms among top athletes is not reflected by asthma diagnosis. As it was expected, our data confirm that – in diagnosis of EIA – lung function testing alone is not useful, whereas reversibility tests are of limited value.

Background: Intensive exercise may affect the innate immunity, influence inflammatory response and increase susceptibility to respiratory infections. Aim: To assess if exercise modifies expression of innate immune response molecules in peripheral blood leukocytes (PBL) of competitive athletes, asthmatics and healthy subjects. Methods: Study included 15 athletes (speed skaters and swimmers), 9 mild-to-moderate asthmatics (AC) and 7 healthy non-exercising subjects (HC).Treadmill exercise challenge was done and PBLs were isolated before, immediately after and 1 hour post-exercise. Following RNA isolation relative gene expression was assessed by qPCR and calculated using 2 -Δ ΔCt method with pre-exercise expression as reference. Results: Significant decrease in mRNA expression immediately post-exercise was observed for IL-1ra in athletes (mean decrease 72%;p Conclusions: Acute exercise decreases innate immune response in PBLs to similar extent in competitive athletes and healthy subjects.

Introduction: Polymorphisms within innate immunity genes are associated with allergic phenotypes but results are variable. These associations were not ana lyzed with respect to allergen exposure. We investigated associations of TLR and CD14 polymorphisms with allergy phenotypes in the context of house dust mite (HDM) exposure. Material and methods: Children, aged 12-16 years ( n = 326), were recruited from downtown and rural locations and assessed by allergist. Skin prick tests, total and HDM-specific sIgE measurements were done. HDM allergen concentrations in dust were measured. Genetic polymorphisms were identified using restric tion fragment length polymorphism (RFLP). Results: Allergic rhinitis, asthma and atopy were more prevalent in urban area. Although HDM allergen concentrations were higher in rural households, sIgE were present more frequently in urban children. In the whole population no association was found between HDM exposure and sensitization. In children with CD14/–159CC, CD14/–159TT and TLR9/2848GA genotypes increased expo sure to HDM was associated with reduced incidence of allergic rhinitis. Signif icant associations of increased HDM exposure with reduced incidence of atopy were found for the whole population and subjects with CD14/–159CC, CD14/–1359GT, TLR4/896AA and TLR9/2848GA genotypes. Among children with CD14/–159CC and CD14/–1359GG significant positive correlation between HDM allergen concentrations in household and sensitization to HDM was observed. In contrast, protective effect of high HDM allergen exposure against specific sensitization was seen in subjects with TLR4/896 AG. Conclusions: Development of specific sensitization and allergy may be associ ated with innate immune response genes polymorphisms and is modified by allergen exposure.

The aim of this study was to compare the efficacy and patient discomfort between four techniques for obtaining nasal secretions. Nasal secretions from 58 patients with symptoms of a common cold, from three clinical centers (Amsterdam, Lodz, Oslo), were obtained by four different methods: swab, aspirate, brush, and wash. In each patient all four sampling procedures were performed and patient discomfort was evaluated by a visual discomfort scale (scale 1-5) after each procedure. Single pathogen RT-PCRs for Rhinovirus (RV), Influenza virus and Adenovirus, and multiplex real-time PCR for RV, Enterovirus, Influenza virus, Adenovirus, Respiratory Syncytial Virus (RSV), Parainfluenza virus, Coronavirus, Metapneumovirus, Bocavirus and Parechovirus were performed in all samples. A specific viral cause of respiratory tract infection was determined in 48 patients (83%). In these, the detection rate for any virus was 88% (wash), 79% (aspirate), 77% (swab) and 74% (brush). The degree of discomfort reported was 2.54 for swabs, 2.63 for washes, 2.68 for aspirates and 3.61 for brushings. Nasal washes yielded the highest rate of viral detection without excessive patient discomfort. In contrast, nasal brushes produced the lowest detection rates and demonstrated the highest level of discomfort.

Background: Cyclooxygenase-1 (COX-1) is a key enzyme involved in generation of prostanoids, important mediators and modulators of asthmatic inflammation. In a subpopulation of aspirin-sensitive asthmatics (ASA) inhibition of COX-1 by nonsteroidal anti-inflammatory drugs results in activation of inflammatory cells and development of symptoms. Alternatively spliced variants of COX-1 lacking 111 bp from exon 9 were described previously but have never been identified in human leucocytes peripheral blood leucocytes (PBL) or upper airway epithelial cells. We aimed to assess the expression of spliced variants of COX-1 mRNA in PBLs from patients with asthma and in healthy subjects (HS) referring the expression to patients characteristics (including ASA-sensitivity) and to aspirin-triggered 15-hydroxyeicosatetraenoic acid (15-HETE) generation. Methods: The study included 30 patients with ASA, 30 patients with aspirin-tolerant asthma (ATA) and 30 HS serving as controls. Nasal polyps for epithelial cell cultures were obtained from 10 patients with chronic rhinosinusitis. Expression of full length and spliced variants of COX-1 enzyme was detected by RT-PCR and presented as the ratio of full-length COX-1 to alternatively spliced COX-1 mRNA [COX-1 alternative splicing index (COX-1 AS index)]. Release of eicosanoids (PGE2 and 15-HETE) by PBLs was measured with enzyme immunoassay. Results: In both PBLs and airway epithelial cells the expression of full-length product prevailed over spliced variants of COX-1 enzyme. Cyclooxygenase-1 AS index was significantly lower in asthmatics as compared to HS (1.96 ± 0.71 vs 2.41 ± 0.99, P

Background Human parainfluenza virus type 3 (HPIV3), while infecting lower airway epithelial cells induces pneumonia and bronchiolitis in infants and children, and may lead to asthma exacerbations in children and adults. Respiratory viruses invading the airway epithelium activate innate immune response and induce inflammatory cytokine release contributing to the pathophysiology of upper and lower airway disorders. However, the effects of HPIV3 infection on nasal epithelial cells have not been well defined. The aim of this study was to evaluate the effect of the HPIV3 infection on cultured human nasal epithelial cells (HNECs) and the release of interferon gamma and other cytokines. Methods RPMI 2650, a human nasal epithelial cell line was cultured into confluence and was infected with HPIV3 (MOI of 0.1, 0.01 and 0.001). The protein release into supernatants and mRNA expression of selected cytokines were assessed 24, 48 and 72 h after infection. Cytokine concentrations in supernatants were measured by ELISA and expression of cytokine mRNA in RPMI 2650 cells confirmed by real time RT-PCR analysis. Results HNECs infection with HPIV3 did not induce cytotoxicity for at least 48 hours, but significantly increased IFN-γ protein concentration in the cell supernatants at 24 h and 48 h post infection (by 387% and 485% respectively as compared to mock infected cells). At 24 h a significant increase in expression of mRNA for IFNγ was observed. RANTES protein concentration and mRNA expression were significantly increased at 72 h after infection (mean protein concentration: 3.5 ± 1.4 pg/mL for 0.001 MOI, 10.8 ± 4.6 pg/mL for 0.01 MOI and 61.5 ± 18.4 pg/mL for 0.1 MOI as compared to 2.4 ± 1.3 pg/mL for uninfected cells). No measurable concentrations of TNF-α, IL-10, TSLP, IL-8, GM-CSF or eotaxin, were detected in virus infected cells supernatants. Conclusions HPIV3 effectively infects upper airway epithelial cells and the infection is associated with induction of IFN-γ and generation of RANTES.

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians, paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation.

Exercise-induced respiratory symptoms are often reported by professional athletes, but asthma and allergy are underdiagnosed. Few studies used standardized questionnaires combined with clinical assessment to investigate asthma and allergy among athletes.Assessment of the prevalence of allergy and asthma symptoms among Polish professional athletes and confronting it with clinical data.Two hundred twenty-two Olympic athletes participated in the project being part of the Global Allergy and Asthma European Network (GA(2) LEN) Olympic study. Allergy and asthma status was determined using Allergy Questionnaire for Athletes (AQUA), spirometry, reversibility test, methacholine challenge and skin prick testing. Final diagnosis was established by an allergist.At least one exercise-induced asthma (EIA) symptom was reported by 28.4% athletes, and finally asthma diagnosis was established in 11.3% while only 5.9% of athletes had history of asthma. Reversibility test was positive in 36% of athletes finally diagnosed with asthma. Allergic rhinitis (AR) symptoms were reported by 27%, and the diagnosis was confirmed in 21% of athletes while only 9% had previously diagnosed AR. No significant differences in frequency of asthma and AR were observed between endurance and non-endurance athletes.High prevalence of exercise-induced respiratory symptoms among top athletes is not reflected by asthma diagnosis. As it was expected, our data confirm that - in diagnosis of EIA - lung function testing alone is not useful, whereas reversibility tests are of limited value.

Background Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens. Methods The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively. Results Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p Conclusions Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein. ispartof: Clinical and Translational Allergy vol:2 issue:1 pages:21- ispartof: location:England status: published

The design of a synthetic jet requires a careful identification of the components' parameters, in order to be able to perform accurate numerical simulations, this identification must be done by mean of a series of measurements that, due to the small dimensions of the components, are required to be non-contact techniques. The activities described in this paper have been performed in the frame of the STA-DY-WI-CO project, whose purpose is the design of a synthetic jet and demonstrate its effectiveness and efficiency for a real application. To measure the energy saving, due to the synthetic jet effects on the separation, the increased performances of the profile must be compared to the energy absorbed by the actuator and the weight of the system. In design phase a series of actuators has being considered as well as a series of cavity layout, in order to obtain the most effective, efficient and durable package. The modal characteristics of piezoelectric component was assessed by means of tests performed with ...

Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity affects from 5 to 30% of adult asthmatics. The diagnosis is established on the basis of anamnesis and confirmed by provocation tests, but the last one carry the risk of serious side effects. There is lack of in vitro test to diagnose NSAID hypersensitivity. The aim of our study was to establish the usefulness of basophil degranulation test in the diagnosis of NSAID hypersensitivity.The study population consisted of 10 patients with aspirin asthma, 6 asthmatics with tolerance of NSAID and 6 healthy subjects. NSAID hypersensitivity was confirmed by aspirin challenge. The level of specific IgE for aspirin was determined in all subjects by ELISA method. Basophil degranulation test (BDT) was performed The BDT was assessed as positive when the basophils degranulation exceeded 30% as compared to control.In all NSAID hypersensitive subjects, sensitivity was confirmed by aspirin challenge. The specific IgE test was negative for all studied subjects. BDT was positive in 9 from 10 NSAID hypersensitive patients and negative in all NSAID tolerant subjects. The positive degranulation was observed in range 10 to 750 microg of aspirin/ml. One false negative result was observed in patient receiving high dose of oral glucocorticosteroids which stabilized basophils and prevent from degranulation.BDT, when performed in increasing aspirin concentration from 50 to 500 microg/ml, seems to be a valuable and safe diagnostic method of NSAID hypersensitivity. The study revealed that sIgE for aspirin are not useful diagnostic method. The study confirmed the involvement of basophils in the NSAID hypersensitivity reaction beyond IgE system.

Background: The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. Methods: Sixty AR patients, aged 18–35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean selfrecorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. Results: Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. Conclusion: Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.

Background Viruses and bacteria are important contributors to asthma exacerbations. Exercise at competitive level is believed to increase susceptibility to respiratory infections. The study aimed at investigation of the anti-infectious immune response in athletes in the context of exercise intensity, atopy and allergic diseases. Methods Questionnaire data were obtained from 219 Polish athletes (median age 26 years) preparing for Beijing Olympic Games during the multicenter study within the GA2LEN project (WP 2.8.2). Allergy Questionnaire for Athletes (AQUA) (Bonini et al 2009) was used to obtain data about symptoms and exercise pattern. Athletes were evaluated by allergist. Control group consisted of 77 healthy never-smokers (median age 29 years) not performing sport at competitive level. Serum IgG against parainfluenza virus 1,2 and 3 (PIV), respiratory syncytial virus (RSV), adenovirus and Mycoplasma pneumoniae were determined by ELISA. Results Percentage of athletes with positive serological testing was lower than percentage of HC in case of PIV (P < 0.0003), RSV (P = 0.01) and M. pneumoniae (P = 0.01). Analysis of IgG only in subjects with positive testing showed lower anti-PIV IgG levels in non-atopic athletes compared to HC (P < 0.001) and atopic athletes (P < 0.01) (median 66.0 vs 104.8 and 88.1 U/mL). In contrast, higher adenovirus IgG titres were found in atopic and non-atopic athletes as compared to HC (52.3 and 48.5 vs 36.6 EIU, P < 0.001). Positive anti-PIV serology test was most frequent in athletes with allergic rhinitis compared to asthmatic and healthy athletes (78.3 vs 50.0 and 46.8%; P = 0.002). For PIV and M. pneumoniae the difference was also seen when atopic and non-atopic athletes were compared separately with HC. Positive RSV serology was more frequent in atopic versus non-atopic athletes (76.3 vs 60.8%, P = 0.03) and in HC versus non-atopic athletes (84.4 vs 60.8%, P = 0.001) but no significant difference between atopic athletes and HC was seen. Positive RSV serology was associated with atopy (OR 2.89; 95% CI, 1.34-6.23; P = 0.007). No differences were observed with regard to exercise pattern (endurance vs non-endurance). Conclusions Competitive sport at Olympic level may be associated with altered immune response against respiratory pathogens. For some agents this response may be affected by the atopic status.