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Rheumatoid arthritis (RA) is a chronic, systemic inflammatory connective tissue disease affecting 0.5–1% of the general population. Interstitial lung disease (ILD) is a serious complication of RA, leads to a deterioration in the quality of life, increases the risk of hospitalization and premature death. The clinical course of RA-associated ILD (RA-ILD) varies from interstitial lesions involving little areas of the lung which do not lead to clinical symptoms, to progressive interstitial lesions that may lead to acute respiratory exacerbation, development of respiratory failure, and death. The main risk factor for the development of ILD in the course of RA, apart from older age and male sex, is the high activity of the underlying disease. Effective treatment of RA, aimed at the goal of remission, may therefore be a preventive method for the development of RA-ILD. Due to non-specific symptoms, the diagnosis of RA-ILD is often overlooked. Despite significant morbidity and increased risk of death due to RA-ILD, currently, we do not have any guidelines on the management of this clinical situation. Moreover, the problem is even more complicated due to the possibility of potential pneumotoxicity of many disease-modifying drugs and their unclear effectiveness regarding lung involvement in RA. Taken together, optimal management of a patient with RA-ILD is a clinical challenge. There is an urgent need to clarify several clinical aspects concerning the early diagnosis, monitoring, establishing indications for treatment, and choice of appropriate therapeutic management. In this work, we performed a scientific review of the current state of knowledge on RA-ILD and indicated the directions of future research needed aiming at improving patients’ care.

Idiopathic inflammatory myopathies (IIM) are rare connective tissue diseases, which can lead to internal organ involvement. IL-33/ST2 pathway is involved in the pathogenesis of numerous diseases including autoimmune disorders. IL-33 fulfils cardioprotective function, while soluble ST2 (sST2) is a decoy receptor that reduces protective impact of IL-33. The aim of the study was to evaluate the concentrations of sST2 and IL-33 in sera of patients with IIM and evaluate its associations with the clinical course of the disease. Patients with IIM as well as age- and sex-matched healthy controls were recruited. Concentrations of sST2 and IL-33 were assessed with ELISA in sera of both patients and controls. Patients were asked to fill in the questionnaires concerning clinical symptoms and physical functioning. Concentrations of sST2 and IL-33 were correlated with the results of laboratory tests and clinical symptoms. Concentrations of sST2 were significantly higher in IIM group than in healthy subjects (median sST2 in IIM 26.51 vs in healthy controls 21.39; p = 0.03). In the majority of patients, IL-33 concentrations did not exceed the detection limit. Anti-SRP-positive patients presented significantly higher concentrations of sST2 as compared to anti-SRP-negative patients (p = 0.04). In patients with anti-Ro52 antibodies, sST2 concentrations were significantly lower than in anti-Ro52-negative patients (p = 0.02). Concentrations of sST2 correlated with the degree of disability evaluated with Health Assessment Questionnaire. sST2 is increased in patients with IIM and its concentration correlates with the degree of disability. In patients with anti-SRP antibodies, levels of sST2 are exceptionally high. Electronic supplementary material The online version of this article (10.1007/s00296-020-04554-z) contains supplementary material, which is available to authorized users.

Introduction Respiratory pathogens are thought to be involved in the pathogenesis and exacerbations of asthma at all ages; however, little is known about the airway microbiome in the elderly. Aim of the study To identify respiratory pathogens in the induced sputum (IS) of elderly asthmatics, and to determine the association between pathogens and the markers of asthma activity. Material and methods Twenty-nine subjects with stable asthma, 15 above 65 years of age and 14 aged 30-49 years, underwent clinical evaluation, fractional exhaled nitric oxide measurement, and sputum induction. Pathogens were detected by multiplex reverse transcription polymerase chain reaction. The periostin concentration of IS supernatants was measured by enzyme-linked immunosorbent assay. Serum eosinophil cationic protein and total IgE levels were measured by ImmunoCAP. Results Elderly patients, as compared to non-elderly, had significantly higher eosinophilia in IS, although other markers of eosinophilic inflammation were comparable. Half of the subjects were positive for Haemophilus influenzae. Chlamydophila pneumoniae was found in two subjects. Respiratory viruses were detected in more than 70% of patients. The detection rates and profiles of atypical bacteria and respiratory viruses were similar in both groups. Only in the elderly asthmatics was influenza A positivity associated with lower predicted FVC%, RSV A positivity connected with decreased tIgE concentration, and RSV B positivity related to a lower percentage of lymphocytes in IS. Conclusions Despite the existence of differences in some clinical and inflammatory characteristics of asthma between elderly and non-elderly asthmatics, the pathogen detection rates in the IS from the two groups are similar.

This review presents a detailed study of original researches and previously published reviews concerning cardiovascular involvement in idiopathic inflammatory myopathies (IIM). We aimed to summarize the current knowledge on the cardiac involvement in IIM, evaluate its impact on mortality and indicate areas still awaiting to be investigated. We searched MEDLINE database (until January 2019) and the reference lists of articles. Selection criteria included only published data, available in English, both original researches and reviews. Articles related to cardiovascular involvement in IIM were selected and analysed. The references were also screened, and relevant articles were included. Cardiovascular involvement is frequent in IIM but typically remains subclinical. Among far less prevalent symptomatic forms, congestive heart failure is the most common. Myocardium and conduction system seems to be predominantly affected. High rate of left ventricular diastolic dysfunction was observed. Non-specific changes of ST-T segment were the most common abnormalities in electrocardiography. Patients with IIM were more frequently affected by atrial fibrillation as compared with other autoimmune diseases. Increased risk of myocardial infarction was observed; furthermore, patients often develop comorbidities that enhance cardiovascular risk. Since cardiovascular disorders remain one of the major causes of death and subclinical involvement is frequent, active screening is justified. Growing availability of the novel imaging techniques may facilitate diagnosis. Correlation between myocardial involvement and the type of autoantibodies and impact of different therapeutic options on the progression of cardiovascular lesions require further studies.

IntroductionIn the course of idiopathic inflammatory myopathies internal organs, including heart and lungs, can be involved. Cardiopulmonary complications significantly alter the course of the disease, leading to poorer prognosis. A lack of clear guidelines on the assessment of internal organ involvement in the course of myositis increases the risk of underdiagnosis. The aim of the study was to evaluate the incidence of clinical symptoms indicative of cardiovascular and pulmonary involvement in patients with myositis, and the impact of these ailments on daily living.Material and methodsA self-designed online survey was distributed via online support groups and community forums for patients with idiopathic inflammatory myopathies. The questionnaire contained inquiries about demographical data, clinical symptoms, including symptoms indicative of cardiopulmonary involvement, as well as the standardised Health Assessment Questionnaire. Respondents were divided according to concomitant diseases into a subgroup diagnosed with cardiopulmonary diseases and a subgroup without such comorbidities. The prevalence of cardiopulmonary symptoms was compared between the subgroups. The impact of cardiopulmonary symptoms on the degree of disability and daily functioning was assessed.ResultsIn total, 370 patients were included in the study group. The most commonly symptoms included dyspnoea during exercise, palpitations and ankle oedema during daily activities. Cardiopulmonary symptoms were frequent in respondents diagnosed with cardiopulmonary diseases and in patients declaring no comorbidities of the heart and lungs. Intensity of chest pain, tolerance of physical activity, and fatigue were comparable in both of the study subgroups. The degree of disability was higher in respondents with concomitant cardiovascular and/or pulmonary comorbidities, but only dry cough and ankle oedema impacted the results.ConclusionsClinical symptoms indicative of heart and lung involvement occur frequently in patients with idiopathic inflammatory myopathies; however, cardiopulmonary complications seem to be relatively rarely detected. Active screening for cardiopulmonary involvement is recommended.

BackgroundThe course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA.MethodsControl and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry.ResultsNo difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p ConclusionSerum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

Bartonella spp. can cause a variety of diseases, such as lymphadenopathies, cat scratch disease, and trench fever, but can also give rise to many non-specific symptoms. No data exists regarding the prevalence of Bartonella spp. in patients with musculoskeletal complaints, nor among blood donors in Poland. The presence of anti-Bartonella IgM and IgG in the serum of blood donors (n = 65) (Lodz, Poland) and in the patients of the Department of Rheumatology Clinic (n = 40) suffering from musculoskeletal symptoms was tested by immunofluorescence. Blood samples were cultured on enriched media. Epidemiological questionnaires were used to identify key potential risk factors, such as sex, age, contact with companion animals, and bites from insects or animals. Altogether, 27 of the 105 tested subjects were seropositive for Bartonella henselae IgG (23%) and three for Bartonella quintana IgG (2.85%); IgMs against B. henselae were found in three individuals (2.85%), and IgMs against B. quintana were found in one (1.54%). No statistically significant difference was found between the prevalence of B. henselae in the blood of donors or patients and the presence of unexplained musculoskeletal complaints (23% vs 30%). Individuals who had kept or been scratched by cats were not more likely to be B. henselae seropositive (p > 0.01). Tick bites were more commonly reported in patients, but insignificantly (p > 0.01). This is the first report of a high seroprevalence of anti-Bartonella IgG in patients with musculoskeletal symptoms and in blood donors in Poland. The obtained results indicate that such seroprevalence may have a possible significance in the development of musculoskeletal symptoms, although it should be confirmed on a larger group of patients. Asymptomatic bacteremia might occur and pose a threat to recipients of blood from infected donors. Hence, there is a need for more detailed research, including molecular biology methods, to clarify the potential risk of Bartonella spp. being spread to immunocompromised individuals. • This is the first study presenting high seroprevalence of Bartonella spp. in Poland. • IgG and IgM antibodies against B. quintana were found in blood samples of blood donors.

An amendment to this paper has been published and can be accessed via the original article.

Background Ankylosing spondylitis (AS) is an insidiously progressive and debilitating form of arthritis involving the axial skeleton, characterized by chronic back pain and progressive spinal stiffness, and lessening of pain and stiffness with exercise. Due to subsequent manifestation in different organs, AS causes reduction in life expectancy, so early diagnosis and treatment are of great importance. No AS cases have been reported in solid-organ transplant recipients yet. Case presentation A 58-year-old woman with end-stage renal disease due to chronic glomerulonephritis, after allogenic kidney transplantation 25 years earlier, with stable, good graft function, treated with chronic immunosuppressive therapy based on cyclosporine A, mycophenolate mofetil, and prednisone, with no previous history of a connective tissue disease presented fever up to 39 °C accompanied by pain localized in sacroiliac region radiating to the left lower limb. Detailed diagnostic procedures and x-rays of the lumbar spine and of the targeted sacroiliac joints revealed lesions characteristic of AS. Sulphasalazine was added to standard immunosuppression regimen with good clinical results. Conclusions We report an adult kidney transplant recipient with a new onset of AS. The risk of relapse or new onset of inflammatory disease in transplant recipients is extremely low due to immunosuppressive therapy following transplantation. However, when it occurs, the clinical presentation is commonly atypical, often leading to delayed diagnosis.

The article discusses pharmacologic and interventional therapeutic options for patients with refractory angina. Refractory angina refers to long-lasting symptoms (≥3 months) due to established reversible ischemia in the presence of obstructive coronary artery disease, which cannot be controlled by escalating medical therapy with second-line and third-line pharmacologic agents, bypass grafting, or stenting. Due to an aging population, increased number of comorbidities, and advances in coronary artery disease treatment, incidence of refractory angina is growing. Although the number of therapeutic options is increasing, there is a lack of randomized clinical trials that could help create recommendations for this group of patients.

The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria, heterogeneity of clinical manifestations, prognostic factors and therapeutic possibilities. PubMed database was screened for "antisynthetase syndrome" OR "antisynthetase antibodies" between February and April 2020. Aminoacyl-tRNA synthetases participate in the immune system activation as antigens, but also serve chemoattractive and cytokine-resembling roles, initiating innate and adaptive pathways. Exposure to various inhaled antigens may induce the autoimmune cascade leading to ASS. NK cells with its impaired INF-y production as well as formation of NETs by neutrophils contribute to pathogenesis. The prevalence of symptoms vary significantly depending on the study with muscular, articular and pulmonary involvement being the most frequently observed. Although classified as subtype of idiopathic inflammatory myopathies, myositis may not necessarily be the prominent manifestation. Since clinical presentation is heterogeneous and symptoms can emerge gradually, ASS could be considered as a heterogeneous spectrum rather than a homogenous disease entity. The currently available classification criteria do not fully correspond with the clinical patterns of the disease. Therapy is based on glucocorticosteroids and other immunosuppressive agents. Randomized controlled trials, dedicated for patients with ASS, are needed to form treatment algorithms.

With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS‐CoV‐2‐induced Coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi‐organ disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies., The authors would like to thank the European Academy of Allergy and Clinical Immunology (EAACI) for the financial support to the sections, interest groups and working groups enabling the development of this paper. The research of SM is supported by a SNSF grant 310039_189334; JSR is funded by Ministerio de Economía y Competitividad (IJCI-2016-27619); KKI is supported by the FWO Post doc mandate 12W2219N; BW and PF were supported by funding from the Istituto Italiano di Tecnologia, Fondazione Telethon (project GGP19103), and Ricerca Finalizzata Giovani Ricercatori 2016 - Ministero Salute Italia (project GR-2016-02362413); GCC is supported by a postdoctoral contract cofounded by the competitive Program “Attracting Talent,” Community of Madrid, Spain; the research of SWCB was funded by DFG (398577603), “ADAPT” EIT Health is a body of the EU receiving support from H2020 and BMBF “ESCAPE” 01KI20169A; the research of UE is supported by the H2020 grant 768641 and by the BMF grant 19056.

Although current therapies in chronic obstructive pulmonary disease (COPD) improve the quality of life, they do not satisfactorily reduce disease progression or mortality. There are still many gaps in knowledge about the cellular, molecular, and genetic mechanisms contributing to pathobiology of this disease. However, increasing evidence suggests that accelerated aging, chronic systemic inflammation, and oxidative stress play major roles in pathogenesis in COPD, thus opening new opportunities in therapy. Therefore, the aim of our review was to describe and discuss some of the most widely used therapeutics that affect the root cause of aging and oxidative stress (metformin, melatonin, sirolimus, statins, vitamin D, and testosterone) in context of COPD therapy.

Atrial fibrillation (AF) is associated with increased risk of thromboembolic complications. One of the markers of the increased risk of hypercoagulable state is platelet hyperreactivity. The aim of the study was to assess impact of arrhythmia on platelet reactivity. Methods The study included 36 (mean age 48,3; range 21–60) male patients with lone atrial fibrillation, with exclusion of concomitant diseases known to trigger hypercoagulable state. The AF patients underwent cardioversion to restore sinus rhythm and were subsequently under observation for 1month. Echocardiography, ECG and blood collection was performed before cardioversion (T0) and 4weeks after successful cardioversion (T1). During the study period patients have been contacted and examined every week and 24h ECG monitoring was performed. Platelet reactivity was assessed based on changes of CD62 and CD42b expression on platelet surface after stimulation with thrombin. Also changes in MPV were assessed. Results In all patients sinus rhythm was maintained at the end of the study period, however in 14 patients recurrences of AF were observed, confirmed by 24h ECG monitoring (atrial fibrillation recurrence group – AFR) and 22 patients maintained sinus rhythm throughout the whole study period (SR group). Mean fluorescence intensity (MFI) of CD62 on thrombin stimulated platelets decreased significantly 4weeks after electrical cardioversion as compared to T0 (48.04±22.42 vs 41.47±16.03; p p Platelets reactivity estimated by CD 62 expression in SR group decreased significantly after 4weeks observation (58.01±15.26 vs 46.57±13.44; p p p p Conclusion The changes of platelet reactivity to thrombin observed after restoration of sinus rhythm in patients prove that arrhythmia intrinsically leads to increased reactivity of platelets.

Background One of the hypothesis of RA pathogenesis is that autoimmune process in rheumatoid arthritis starts within the airways. The factors leading to increased antiCCP antibodies formation within the airways are not fully understood. People with allergies to inhaled allergens suffer from chronic inflammation within upper and lower airways. Objectives The aim of this study was study was to assess the prevalence of symptoms of upper and lower airways allergic diseases in patients with rheumatoid arthritis as compared to general population prevalence. Methods The study group consisted of 96 patients with RA (age years – 46,69±15,70 women-93%, men – 7%). Control group consist 1685 subjects from Lodz population (47,89±15,11 women-55%, men-45%). All responders completed a screening test for allergy symptoms, 60 of RA and all controls were asked to complete a detailed survey consisting of 30 questionnaires based on GA2LEN Global Allergy and Asthma Network protocol include diagnoses and separate symptoms of allergic diseases. Results In screening questionnaire 16,84% of RA patients and 7,24% control declare that suffer from asthma (p 0,05), however the coexistence of dyspnoea and wheezing was more frequent in the group of patients with RA (44,83% vs 14,01%; p The symptoms of upper airway chronic inflammation were also more prevalent in patients with RA as compared to controls. Chronic sinusitis was declared by 26,67% of patients and 10,62% controls (p Conclusion Increased prevalence of symptoms of upper and lower allergic diseases in patients with RA requires further investigation as chronic inflammation within airways can lead to posttranslational modification of proteins and autoantigen formation. Disclosure of Interests None declared

Background Cardiovascular involvement in patients with idiopathic inflammatory myopathies (IIM) significantly worsen the prognosis and remain one of the major cause of death1. Although it is usually subclinical, symptomatic manifestations are not infrequent and exert considerable impact on the course of IIM2. Objectives To evaluate the frequency of subjective symptoms indicating cardiovascular involvement in patients with different subtypes of IIM and assess the impact of such ailments on daily living and degree of disability. Methods An online questionnaire was created and distributed by means of online support groups to English-speaking patients with IIM. Responders were asked to answer 40 questions concerning subtype and duration of disease, cardiac and musculoskeletal symptoms as well as to fill the Short 2-page Health Assessment Questionnaire (HAQ). Responses of patients with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and overlapping syndrome (OS) were analysed statistically. Results Questionnaire was completed by 377 responders, among which 38,78% had IBM, 34,07% DM, 16,62% PM and 10,53% OS. Dyspnoea at rest affected at least a few times a month 48,33% patients with PM, 43,09% with DM, 28,95% with OS but only 20,71% with IBM (PM vs OS p=0,057, IBM vs DM p Conclusion Symptomatic cardiovascular involvement is frequent in patients with IIM. Patients with IBM are less affected by cardiac symptoms yet present the highest degree of disability. Most of cardiac symptoms do not aggravate disability. References [1] Diederichsen LP, Cardiovascular involvement in myositis, Curr Opin Rheumatol. 2017Nov;29(6):598-603 [2] Diederichsen, LP, et al., Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities, Arthritis Care Res (Hoboken). 2016Jul;68(7):1012-20 Disclosure of Interests None declared

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder with not fully elucidate pathogenesis. Rheumatoid arthritis patients have increased risk of developing lymphomas. One of the possible mechanisms of this predisposition is increased genomic instability and impaired DNA repair. It is unclear how this genomic instability contributes to diseases pathogenesis. Objectives: The aim of this study was to analyze the sensitivity and repair efficiency of mononuclear cells isolated from RA patients to DNA damaging agents. Methods: The study group consisted of 22 patients with RA (age years - 60,77±13,00 women-17, men - 5) hospitalized in the Department of Rheumatology between 2017 and 2018 and 10 healthy controls without autoimmune and oncological diseases in clinical history (age 44,09±16,56; women-5, men-6). The peripheral blood mononuclear cells (PBMC) from all subjects were isolated. Using comet assay the degree of intracellular DNA damage as a result of exposure to standard damage factors: tert-butyl hydroperoxide (TBH), bleomycin, methyl methanesulfonate (MMS) and UV radiation was assessed. Results: RA patients show a statistically significant higher level of endogenous damage in PBMC DNA than controls (mean RA- 8,64% vs 4,68% in control; p Conclusion: DNA of people with rheumatoid arthritis is significantly more susceptible to damage in baseline and induced. The kinetics of DNA repair from RA patients after the introduction (TBH and bleomycin) was statistically less effective as compared to healthy control. Understanding the ethology of this phenomenon in RA may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Acknowledgement: The project is financed under the funds of the National Science Center (2017/25/B/NZ6/01358) Disclosure of Interests: None declared

Idiopathic inflammatory myopathies (IIM) are progressive, debilitating diseases that can lead to severe impairment. The aim of the study was to evaluate the level of disability and compare it between different subtypes of IIM as well as to estimate clinical symptoms associated with greater risk of disability and distinguish the most troublesome activities in this group of patients. A online form concerning clinical symptoms, comorbidities and limitations in daily living was created and distributed to online support groups for patients with IIM. Health Assessment Questionnaire was used to estimate disability and physical limitations while visual analogue scales enabled to assess the intensity of clinical symptoms. 361 out of 377 responders were included for further evaluation. High prevalence of disability was observed in each subtype yet predominantly in patients with inclusion body myositis (IBM) as 51.43% of them fulfilled the criteria of severe to very severe disability. Level of disability correlated with muscle weakness, tolerance of physical activity and level of fatigue. 45.62% of responders in general required walking devices and 43.50% of participants declared using facilitating devices for maintaining hygiene. Patients with IIM encounter multitude physical limitations that can be partially compensated by usage of facilitating devices or aid of the caregivers. IBM seems to be the most disabling subtype.

Gout, known as “the disease of the kings”, is the most frequent type of arthritis. It results from sustained hyperuricemia that leads to monosodium urate crystal deposition in joint structures and soft tissue. Environmental factors such as diet affect the incidence of gout; there is a known relationship between the occurrence of an acute attack of gout and the consumption of alcohol and meat; and a low purine diet is a widely recognized nonpharmacological method of supplementing the treatment and preventing recurrence of arthritis. This review aims to summarize the current knowledge about the role of vitamin C in prevention and treatment of gout. A PubMed/Medline database search on the role of vitamin C in purine metabolism was done. Reports from in vitro and animal studies seem to be promising and to allow explanation of the physiological relationship between vitamin C and uric acid. Most epidemiological studies indicate a significant correlation between high vitamin C intake and lower serum uric acid levels. Despite promising observations, there are few observational and interventional studies, and their results do not clearly define the benefits of a high daily intake of vitamin C in preventing the development and recurrence of gout.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

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.

Osteoporosis and associated low energy fractures are a significant clinical problem, especially in the elderly population. The occurrence of a hip fracture is associated with significant mortality and a high risk of disability. For this, apart from the treatment of osteoporosis, effective prevention of both the development of the disease and related fractures is extremely important. One aspect of osteoporosis prevention is proper dietary calcium intake and normal vitamin D3 levels. However, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention, too. This review aims to summarize the current knowledge about the role of vitamin C in osteoporosis development, prevention and treatment. The PubMed/Medline search on the role of vitamin C in bone metabolism database was performed for articles between 2000 and May 2020. Reports from in vitro and animal studies seem promising. Epidemiological studies also indicate the positive effect of high vitamin C content in the daily diet on bone mineral density. Despite promising observations, there are still few observational and intervention studies and their results do not allow for unequivocal determination of the benefits of high daily intake of vitamin C or its long-term supplementation.

Background:Scleroderma can significantly impair daily functioning by leading to multi-organ involvement and profound fatigue. Recent studies suggest that objective measures of the disease severity may not necessarily correspond with the patients’ perception1.Objectives:To evaluate the degree of disability and fatigue in patients with scleroderma, distinguish the most troublesome activities and assess which clinical symptoms had mostly impact on daily functioning.Methods:An online questionnaire was created and distributed to English-speaking patients with scleroderma by means of online support groups. The questionnaire contained inquiries about demographical data, clinical symptoms as well as the Scleroderma Health Assessment Questionnaire (SHAQ, comprised of HAQ-DI and specific VAS scales) and Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F). Standard and Alternative Disability Indexes (SDI and ADI) were counted based on answers in HAQ-DI part. Degrees of disability and fatigue, reflected by SDI, ADI and FACIT-F scores, were compared between subgroup of patients with and without particular clinical symptoms. Responses were analysed statistically.Results:Questionnaire was completed by 85 responders (mean age 48,93±14,4; 98,82% were female). Mean SDI was 1.09±0.66 with 41.18% of patients fulfilling the criteria of mild to moderate difficulty (SDIConclusion:Majority of patients with scleroderma are moderately to severely disabled yet cope with the impairments with the widespread use of facilitating devices or aid of caregivers. Profound fatigue, observed in the majority of patients, may contribute to the high overall perception of disease severity.References:[1]Jaeger VK, Distler O, Mauer B et al. Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group. Rheumatology (Oxford). 2018 Mar 1;57(3):441-450. doi: 10.1093/rheumatology/kex182Disclosure of Interests:None declared

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.

Obstructive sleep apnea is a chronic condition characterized by recurrent episodes of apneas or hypopneas during sleep leading to intermittent hypoxemia and arousals. The prevalence of the sleep disordered breathing is estimated that almost 50% of men and 24% of women suffer from moderate to severe form of the disorder. Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates. Platelets participate in the process of transcellular production of bioactive lipids by delivering both specific enzymes and substrate molecules. Despite their lack of nucleus, platelets synthetize proteins in a stimuli-dependent manner. Atherosclerosis and consequent cardiovascular complications result from disruption in homeostasis of both of the platelet roles: blood coagulation and inflammatory processes modulation. Platelet parameters, routinely evaluated as a part of complete blood count test, were proposed as markers of cardiovascular comorbidity in patients with obstructive sleep apnea. Platelets were found to be excessively activated in this group of patients, especially in obese subjects. Persistent activation results in enhanced spontaneous aggregability and change in cytokine production. Platelet-lymphocyte ratio was suggested as an independent marker for cardiovascular disease in obstructive sleep apnea syndrome and continuous positive air pressure therapy was found to have an impact on platelet parameters and phenotype. In this literature review we summarize the current knowledge on the subject of platelets involvement in obstructive sleep apnea syndrome and consider the possible pathways in which they contribute to cardiovascular comorbidity.

Despite their low frequency, drug hypersensitivity reactions (DHRs) can be serious and result in lifelong sequelae. The diagnosis is critical to avert future reactions and should identify the culprit drug or drugs and safe alternatives. However, making the diagnosis can be complex and challenging. Reliable in vitro tests can offer the potential to improve a diagnosis of DHR and influence medical decision making. Importantly, in vitro testing is frequently not performed as a test in isolation but rather as a component of a diagnostic algorithm along with additional tests. There are several in vitro approaches for the different endotypes of DHRs. However, only few are available for routine diagnosis, and many are restricted to research laboratories. In vitro tests exhibit varying sensitivity and specificity depending on the drug involved and the clinical phenotype. In vitro tests can complement skin tests, especially in patients with negative or equivocal skin test responses inconsistent with the clinical presentation and in severe reactions in which drug provocation tests are contraindicated. The main unmet need for many in vitro tests for the diagnosis of DHRs is validation in larger studies with standardized controls that could harmonize diagnostic management between the United States, European Union, and other regions of the world.

Background Idiopathic inflammatory myopathies (IIM) being one of the connective tissue diseases are a group of diseases with not fully understood pathology. The common features are production of autoantibodies, abnormal immune response against self-antigens and inflammatory process leading to destruction of muscle cells and internal organ involvement. Patients with inflammatory myopathies have higher risk of developing cancers. One of the processes that can attribute to increased risk of cancers can be genomic instability and impaired DNA repair. Objectives The aim of the study was to assess the processes of endogenous and exogenous DNA damage and its repair in patients with IIM as compared to healthy controls. Methods The study included 10 patients (9 men and 1 woman, mean age 46,6±16,5) with idiopathic inflammatory myopathies (dermatomyositis or polymyositis) as well as 7 healthy control individuals (4 men and 3 women, mean age 33,8±9,8). DNA damage and repair were investigated by the comet assay. To perform the comet assay human peripheral blood mononuclear cells (PBMCs) were isolated and incubated with tert-butyl hydroperoxide (t-BOOH) or bleomycin. Both compounds are common DNA damaging agents – t-BOOH induces oxidative DNA lesions whereas bleomycin induces also DNA double strand breaks (DSBs). To test the DNA repair capability, PBMCs were allowed to recover for 2 hour. The level of endogenous DNA lesions was also investigated. Results The levels of endogenous DNA damage were not statistically significantly different between tested groups (IIM-3,3±3,6% vs 3,2±3,8% in control; p=0,648). The extent of the DNA damage induced by bleomycin (IIM-23,3±19,5% vs 9,8±5,9% in control) as well as oxidative stress (IIM-14,7±16,2% vs 10,4±7,4% in control) was significantly higher in PBMS derived from IIM patients than in healthy counterparts (p Conclusions Understanding the etiology of this phenomena in these diseases may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Finding the patients with increased DNA instability could potentially serve as a biomarker and indicate the group of patients who should be carefully screened for neoplasmatic disorder. Disclosure of Interest None declared

Background Psoriatic arthritis (PsA) is affecting up to 40% of the patients with psoriasis. The pathogenesis of PsA in not completely understood. One of the hypothesis suggest that repeated micro injuries and trauma and lack of proper inhibition of inflammation lead to chronic inflammation spreading to surrounding tissue and other joints and ligaments. One of the mediators which lead to inhibition of inflammation in healthy conditions are derivatives of arachidonic acid – lipoxins. Objectives The aim of the study was to assess if the influence of lipoxin A4 on inhibition of synthesis of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMNCs) of patients with psoriatic arthritis. Methods The study group consisted of 10 patients with psoriatic arthritis and 5 healthy controls. The peripheral blood mononuclear cells from patients with PsA and healthy controls were isolated and were stimulated with lipopolisacharide (LPS) with or without 200 nM of lipoxin A4 for 24 hours. The supernatants were collected after 24 hour stimulation. The levels of IL-1b, IFN-gamma, TNF alfa, MCP-1, IL-6, IL-8 and IL-33 were assessed by cytometric bead array system. Results Incubation of cells with LPS, increased production of all cytokines assessed either in patients with psoriatic arthritis or in healthy controls. In PBMCs from healthy controls incubation of cells with lipoxine A4 decrease production of proinflammatory cytokines (IL-1b, MCP-1, IL-8, IL-6, IL-33 and TNF-alfa; p Conclusions Our study demonstrated that modulation of Inflammation by lipid mediatiors in patients with psoriatic arthritis is dysregulated. Disclosure of Interest None declared

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs and are among the major causes of hypersensitivity reactions. NSAIDs can evoke different types of both immunological and non-immunologically mediated hypersensitivity reactions, and management of these reactions depends on type of hypersensitivity reaction. As NSAIDs are comprised of several drugs with different chemical structures which can inhibit both cyclooxygenases or selectively cyclooxygenase type 2 (COX-2), in most of the cases, it is possible to find a safe non-cross-reactive drug for a patient. However, in certain situations, especially when patients require anti-platelet treatment, patients can be desensitized to aspirin.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common cause of drug hypersensitivity reactions (DHR). Recent studies show that the prevalence of hypersensitivity reaction to drug is particularly in Poland. Objectives To assess the frequency and the risk od developing NSAID hypersensitivity in patients with chronic disorders of the musculoskeletal system. Methods The study group consisted of 200 patients (age 19–88 years - 54,5±14, women-161, men-39) hospitalized in the Department of Rheumatology in 2015–2016. All patients filled questionnaire regarding symptoms of DHR after ingestion of non-steroidal anti-inflammatory drugs. The presence of DHR, clinical pattern of the reaction, frequency of NSAIDs administration and comorbidities have been studied. In statistical studies the main risk factors were defined. Results Seventy-seven patients from study group (38,5%) reported symptoms that occurred within 24 hours after NSAIDs ingestion. Symptoms characteristic for hypersensitivity reaction were reported by 40 patients (20%). Respiratory symptoms like dyspnea and/or cough were reported by 22 patients (11%). Cutaneous symptoms (urticaria/angioedema/dermal flush) were reported also by 29 patients (14,5%). Three patients experienced loss of consciousness. Thirty-seven patients reported isolated stomach cramps. The symptoms developed usually between 2–12 hours after drug intake. In 37 patients oral administration caused DHR reaction, moreover in 14 patients also topical application led to adverse reaction. In most of patients reaction appeared due to COX-1 inhibitor and interestingly in 3 patients reaction was evoked by celecoxib which is perceived to be safe alternative for patients with NSAIDs hypersensitivity. Chronic urticaria, asthma and systematic drug intake occurs the main risk factors of hypersensitivity. Conclusions Drug hypersensitivity reactions are reported very frequently in population of patients with chronic musculoskeletal disorders. Our studies suggest that patients taking protractedly NSAIDs are in group with high risk of drug hypersensitivity development. Disclosure of Interest None declared

Background Osteoporosis is a major cause of morbidity and mortality in elderly population. It is known that the mortality rate in European population within 1 year of hip fracture is about 30%, and another 30% of patients need long term nursing for the rest of their life. However, the prevalence and associated risk factors in the Polish elderly population have not been well documented. The aim of the study was to assess prevalence of osteoporosis in Polish elderly population and to assess risk factors related to osteoporotic fractures Objectives The study was based on questionnaires distributed among 645 students (61 men, 533 women and 51 not report mean age 69,42±5,88) attending the Healthy Aging Academy at Medical University. Methods Students were asked to answer 20 questions including information about endured fractures, osteoporosis risk factors, screening densitometry, treatment of osteoporosis, supplementation with vitamin D3 and calcium. Also, questions about classical risk factors for osteoporosis (loss of height (5 cm/year), family history, falls, loss of weight, treatment with steroids) were included to questionnaire. Results Fractures caused by fall from their own height were reported by 180 (27,91%). Moreover, 96 (14,88%) responders without fracture history declared more than 3cm decrease of height after their forties, what strongly suggest osteoporotic vertebral fractures. Forty three (24%) of the respondents had multiple fractures and single fractures were reported by 137 (76%) respondents. The most common localization of fractures was forearm (57%), shin bones (10,4%) and foot bones (9%). Among subjects who underwent densitometry after the fracture 32% had the diagnosis of osteopenia; 19,4% were diagnosed with osteoporosis and in 23,1% bone density was within normal limits. The strongest risk factors for osteoporotic fractures were numerous falls per year (p=0,000) and frequent drinking of alcohol (p=0,008). The risk factors of fractures (sum of risk factors for falls and osteoporosis) among people with previous fractures vs. those without fractures were statistically significant (p=0,037). Only 13% of patient with fracture and 15% of all patients with osteoporosis and osteopenia were treated by antiosteoporotic drugs (ibandronian/aledronian). Calcium supplementation was received by 30% of patients with fracture and 43% supplemented vitamin D3. Conclusions The prevalence of osteoporotic fractures in population of relatively well educated population of participants of Third Age University seems to be high. Patients with osteoporosis do not receive appropriate pharmacological prophylactic treatment, pointing at the need for education of primary care physicians and elderly population about burden and consequences of osteoporosis. Disclosure of Interest None declared

Lambda interferons (IFNLs) have immunomodulatory functions at epithelial barrier surfaces. IFN-λ4, a recent member of this family is expressed only in a subset of the population due to a frameshift-causing DNA polymorphism rs368234815. We examined the association of this polymorphism with atopy (aeroallergen sensitization) and asthma in a Polish hospital-based case-control cohort comprising of well-characterized adult asthmatics (n = 326) and healthy controls (n = 111). In the combined cohort, we saw no association of the polymorphism with asthma and/or atopy. However, the IFN-λ4-generating ΔG allele protected older asthmatic women (>50 yr of age) from atopic sensitization. Further, ΔG allele significantly associated with features of less-severe asthma including bronchodilator response and corticosteroid usage in older women in this Polish cohort. We tested the association of related IFNL locus polymorphisms (rs12979860 and rs8099917) with atopy, allergic rhinitis and presence/absence of asthma in three population-based cohorts from Europe, but saw no significant association of the polymorphisms with any of the phenotypes in older women. The polymorphisms associated marginally with lower occurrence of asthma in men/older men after meta-analysis of data from all cohorts. Functional and well-designed replication studies may reveal the true positive nature of these results. SC was supported as a visiting scientist by Healthy Ageing Research Centre, Medical University of Lodz. This study was supported by Polish National Science Centre grant no. 2013/09/B/NZ6/00746 . The authors (SC, AW, MP, JM and MLK) have been partially supported by The Healthy Ageing Research Centre Project (REGPOT-2012-2013-1, 7FP). Inter99 and Health2006 study: TS was supported by a grant from the Lundbeck Foundation (Grant number R165-2013-15410), the Harboe Foundation (Grant number 16152), the A.P. Møller Foundation for the Advancement of Medical Science (Grant number 15-363), Aase and Einar Danielsen's Foundation (Grant number 10-001490), and the Weimann's grant. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). GERA study: This work has been sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). COPSAC2000 study: We greatly acknowledge the private and public research funding allocated to COPSAC and listed on www.copsac.com, with special thanks to The Lundbeck Foundation (Grant nr. R16-A1694); Ministry of Health (Grant nr. 903516); Danish Council for Strategic Research (Grant nr.: 0603-00280B); The Danish Council for Independent Research and The Capital Region Research Foundation as core supporters.

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs.

International audience; Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because invivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available invitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these invitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available invitro methods for DHR diagnosis. We have found that although there are many invitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available invitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

Background Several proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling. The aim of the study was to compare the concentration of proangiogenic factors in the sera of asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity. Methods Serum was collected from 45 patients with severe/refractory asthma (SRA) and 51 patients with non-severe asthma (nSA). The control group included 30 HS. Serum concentrations of Angiopoietin-1, Angiopoietin-2, vascular endothelial growth factor (VEGF) and osteopontin were assessed by the enzyme-linked immunosorbent assay. Results The levels of Angiopoietin-1 (68.8 ± 2.7 vs 56.4 ± 9.3 ng/ml; p

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders.METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires.RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis.CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

To cite this article: Tomassen P, Newson RB, Hoffmans R, Lotvall J, Cardell LO, Gunnbjornsdottir M, Thilsing T, Matricardi P, Kramer U, Makowska JS, Brozek G, Gjomarkaj M, Howarth P, Loureiro C, Toskala E, Fokkens W, Bachert C, Burney P, Jarvis D. Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis – a GA2LEN study. Allergy 2011; 66: 556–561. Abstract Background: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA2LEN European survey. Methods: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. Results: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (−3.0%, 95% CI: −5.0 to −1.0%, I2 = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Conclusion: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.

Background: Demographic and immunological determinants of severe refractory asthma (SRA) are not well characterized. Because Staphylococcus aureus enterotoxins with superantigenic activity have been associated with upper and lower airway inflammation, we aimed to evaluate the association of sensitization to Staphylococcal enterotoxins with asthma severity and various asthma phenotypes. Methods: The study included 109 patients with SRA diagnosed according to the American Thoracic Society Workshop 2000, and 101 patients with nonsevere asthma, followed for at least 12 months. Specific IgE to Staphylococcus enterotoxins and total IgE and eosinophil cationic protein concentrations were measured in serum with immunoassays. Findings: A significant risk for severe asthma was associated with female gender [Odds Ratio (OR) = 2.04], history of wheezing in childhood (OR = 2.47), presence of hypersensitivity to aspirin (OR = 1.96) and with body mass index (OR = 3.08). The mean level of enterotoxin-specific IgE was 3-fold higher in patients with severe asthma when compared to patients with nonsevere asthma (P = 0.01). Serum-specific IgE to enterotoxins was significantly associated with low respiratory function parameters (FEV1, FEV1/FVC and MEF 25/75) and increased airway reversibility in response to albuterol. The presence of specific IgE to enterotoxin carried a significant risk for patients to have serum total IgE level above 100 kU/l (OR = 7.84). Interpretation: Specific immunological response to enterotoxins is associated with clinical and immunological parameters of asthma severity, suggesting a role for Staphylococcal enterotoxins in the asthma pathogenesis.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

The aim of this study was to assess the association of severe exacerbations of asthma and Chronic Obstructive Pulmonary Disease (COPD) requiring ambulance emergency service (AES) visits with meteorological parameters and influenza outbreaks.The records of patients calling the AES in 2007 and 2008 in the urban area of Lodz due to dyspnea were analyzed. Information on 25 daily reported meteorological parameters was obtained from the local meteorological service and data on influenza outbreaks obtained from the national surveillance service.During the winter months, a significantly higher mean daily number of AES visits for both COPD and asthma were noticed when compared to the summer. Interestingly, the number of daily AES visits correlated with several weather parameters, and the multiple regression analysis confirmed a negative correlation with minimum temperature, mean temperature and the dew point for both diseases (R = 0.526; p0.01; R = 0.577; p0.01 and R = 0.589; p0.01). Furthermore, the increased number of AES visits also correlated with a new number of cases of influenza infections as reported by local influenza surveillance system (rs = 77.6%; p0.001 and rs = 80.8%; p0.001 for asthma and COPD, respectively).Seasonality of AES visits for asthma and COPD are similar and seems to be related to specific weather conditions and to influenza outbreaks.

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.