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1.
  • Eldh, Maria, 1980, et al. (author)
  • MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
  • 2014
  • In: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
  • Journal article (peer-reviewed)abstract
    • Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
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2.
  • Ermis, Özuygur, 1991, et al. (author)
  • Sensitization patterns to cat molecular allergens in subjects with allergic sensitization to cat dander
  • 2023
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 13:8
  • Journal article (peer-reviewed)abstract
    • The use of molecular allergology has increasingly become common in the diagnosis and management of allergic diseases. However, there is still a lack of data on cat molecular allergens in adults. Therefore, we aimed to uncover the sensitization patterns to cat molecular allergens.Participants were recruited from the West Asthma Sweden Study, a population-based study enriched with asthma subjects aged 16-75years. Of 1872, 361 individuals were positive for cat dander immunoglobulin E and were further analysed for cat molecular allergens (Fel d 1/2/4/7). Sensitization patterns were classified as monosensitization, polysensitization, and concomitant sensitization, and were related to demographic and clinical measurements.Among cat-sensitized subjects, 84.2% were sensitized to secretoglobin, while 42.4% were sensitized to lipocalins. Nearly half of the subjects were monosensitized to Fel d 1. Polysensitization was observed in 20.2%, and concomitant sensitization to protein families was seen in 7.2%. Asthma prevalence, cat exposure, and rural living were associated with poly- and concomitant sensitization to protein families. Concomitant sensitization to single allergens was more common in those with asthma than in those without, while concomitant sensitization to both Fel d 1 and Fel d 4 was the most common pattern in individuals with asthma. Sensitization patterns also differed according to cat ownership and the degree of urbanization.Sensitization to molecular allergens was observed in 90.9% of cat-sensitized subjects and showed variations across participants' background characteristics and the presence of asthma. Identification of sensitization patterns to cat allergens might provide better characterization of cat-allergic subjects.
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3.
  • Ermis, Özuygur, 1991, et al. (author)
  • Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study
  • 2023
  • In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894 .- 1365-2222. ; 53:1, s. 88-104
  • Journal article (peer-reviewed)abstract
    • As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes, and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population.Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5, Can f 6 using ImmunoCAPTM . Poly-sensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin, or prostatic kallikrein).Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without.Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.
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4.
  • Kämpe, Mary, 1956-, et al. (author)
  • Upper airway and skin symptoms in allergic and non-allergic asthma: Results from the Swedish GA(2)LEN study
  • 2018
  • In: Journal of Asthma. - Abingdon : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 55:3, s. 275-283
  • Journal article (peer-reviewed)abstract
    • Background: Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups. Methods: This cohort (age 17-76years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire. Results: Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01). Conclusion: Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.
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5.
  • Nwaru, Bright I, et al. (author)
  • Furry Animal Allergen Component Sensitization and Clinical Outcomes in Adult Asthma and Rhinitis
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 7:4, s. 1230-1238.e4
  • Journal article (peer-reviewed)abstract
    • Background: Sensitization to allergen components has been linked to asthma in children, but studies in adults are lacking.Objective: To study the relation of sensitization to furry animal allergen components to risk of asthma, rhinitis, and markers of asthma severity in adults.Methods: From the West Sweden Asthma Study, a random population-representative sample of adults aged 16 to 75 years, 2006 participants were clinically examined; 1872 were analyzed for serum IgE level to a mix of aeroallergens. Those with an IgE level of more than 0.35 kUA/L to cat, dog, or horse allergen components were analyzed for specific cat (Felis domesticus [Fel d 1, Fel d 2, and Fel d 4]), dog (Canis familiaris [Can f 1, Can f 2, Can f 3, and Can f 5]), and horse (Equus caballus [Equ c 1]) allergen components. We defined monosensitization, double sensitization, and polysensitization (>2 components) patterns and applied cluster analysis to derive distinct sensitization clusters.Results: Sensitization to each allergen component, lipocalins, each sensitization pattern, and each sensitization cluster (nonsensitized, Fel d 1–driven sensitized, and multisensitized clusters) was associated with substantial increased risk of asthma, rhinitis, concomitant asthma and rhinitis, and Asthma Control Test–controlled asthma. Fel d 1, Can f 1, Can f 2, Can f 3, polysensitization, and multisensitized cluster were further associated with increased fractional exhaled nitric oxide and eosinophil levels, but with lower PD20 methacoline (provocative dose of methacholine causing a 20% drop in FEV1) values. There was no association with asthma exacerbations, FEV1 predicted values, emergency visits or regular oral steroid use, and neutrophil levels.Conclusions: Sensitization to furry animal allergen components is an important predictor of asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide, and airway hyperreactivity.
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6.
  • Papadopoulos, Nikolaos G, et al. (author)
  • Research needs in allergy: an EAACI position paper, in collaboration with EFA.
  • 2012
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
  • Journal article (peer-reviewed)abstract
    • ABSTRACT: 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.
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7.
  • Suzuki, Shintaro, et al. (author)
  • Characterization of sensitization to furry animal allergen components in an adult population.
  • 2019
  • In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222 .- 0954-7894. ; 49:4, s. 495-505
  • Journal article (peer-reviewed)abstract
    • There are paucity of data on sensitization to furry animal allergen components in adults. Furry animals are major sensitizers and contributors to asthma burden in northern Europe and North America.To characterize sensitization patterns to furry animal allergen components in Swedish adults.Based on the West Sweden Asthma Study, a random population (n=1103) and an asthma sample (n=769) were tested for allergen sensitization using Phadiatop® . Those with IgE≥0.35kUA /L were tested for cat (Fel d 1, 2, and 4), dog (Can f 1, 2, 3, and 5), and horse (Equ c 1) allergen component sensitization. We defined allergen component poly-sensitization patterns, identified data-driven sensitization clusters, described component sensitization overlaps, and assessed determinants of sensitization patterns.The prevalence of allergen component sensitization ranged from 0.8% for Fel d 2 and Can f 3 to 8.9% for Fel d 1. The most common dog component was Can f 5 (3.6%); 2.1% were sensitized to Equ c 1. Those sensitized to Fel d 2 and Fel d 4 were commonly sensitized to Fel d 1. The most common dog component overlap was between Can f 1/Can f 2 and Can f 5. Mono-sensitization was 5.6%, double sensitization 1.5% and poly-sensitization 2.1%. Sensitization was always higher in the asthma than in the random sample. Three sensitization clusters were derived, namely non-sensitized (90% in random vs 66% in asthma sample); Fel d 1-driven sensitized (7% vs 19%); and multi-sensitized (3% vs 15%). Key determinants of sensitization were gender, age, raised on a farm, family history of allergy or asthma, smoking, and occupational exposure to dust or fumes.Fel d 1 and Can f 5 are the most common cat and dog components sensitization in this adult Swedish population. Mono-sensitization is more common than poly-sensitization. This detailed characterization highlights the current distribution of furry animal allergen components in Swedish adults, and their impact on clinical outcomes of asthma will be further explored.
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8.
  • Admyre, C, et al. (author)
  • Exosomes - nanovesicles with possible roles in allergic inflammation.
  • 2008
  • In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 63:4, s. 404-8
  • Research review (peer-reviewed)abstract
    • Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
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9.
  • Ankerst, J., et al. (author)
  • Comparison of the bronchodilating effects of formoterol and albuterol delivered by hydrofluoroalkane pressurized metered-dose inhaler
  • 2005
  • In: Treat Respir Med. ; 4:2, s. 123-7
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To compare the onset of bronchodilation with a new formoterol hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) with albuterol (salbutamol) HFA pMDI. PATIENTS AND METHODS: Thirty patients with stable mild or moderate asthma (23 using inhaled corticosteroids, mean FEV(1) 82% of predicted, >or=15% reversibility to terbutaline 1mg after 30 minutes) received formoterol HFA (Oxis) 2 x 4.5microg, albuterol HFA (Ventoline) Evohaler) 2 x 100microg, or placebo at three separate visits in this randomized, double-blind, double-dummy, three-way crossover study. FEV(1) was measured before and 3, 10, 20, 30 and 60 minutes after inhalation. Change in FEV(1) at 3 minutes after inhalation was the primary variable. RESULTS: Mean baseline FEV(1) was stable on all study days (range 2.92-2.94L). FEV(1) values at 3 minutes were: formoterol 3.22L (8% increase), albuterol 3.23L (9% increase) and placebo 2.99L (both p < 0.001 vs placebo). Maximum FEV(1) increased similarly with formoterol and albuterol, with no differences observed between the active treatments at any time point. Patients rated treatment effective at 3 minutes in 15 of 30, 19 of 30 and 7 of 30 cases with formoterol, albuterol and placebo, respectively. All treatments were well tolerated. CONCLUSION: In stable, mild, or moderate asthma, formoterol 9microg and albuterol 200microg, both by HFA pMDI, provided equally rapid and effective bronchodilation.
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10.
  • Axelsson, Malin, 1964-, et al. (author)
  • A personality and gender perspective on adherence and health-related quality of life in people with asthma and/or allergic rhinitis.
  • 2014
  • In: Journal of the American Association of Nurse Practitioners. - : Ovid Technologies (Wolters Kluwer Health). - 2327-6886 .- 2327-6924. ; 26:1, s. 32-39
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Poor adherence to medication treatment for asthma and allergic rhinitis could challenge a positive health outcome. Health-related quality of life (HRQL) is an important measure of health outcome. Both personality and gender could influence adherence and perceptions of HRQL. The purpose was to clarify the role of personality and gender in relation to adherence and HRQL in people with asthma and/or rhinitis.DATA SOURCES: Participants (n = 180) with asthma and allergic rhinitis, selected from a population-based study, filled out questionnaires on the five-factor model personality traits-neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness-HRQL, and adherence to medication treatment. Data were statistically analyzed using t-tests, Mann-Whitney tests, bivariate correlations, and multiple regressions.CONCLUSIONS: Personality traits were associated with adherence to medication treatment in men. The influence of personality traits on HRQL also differed between men and women. These differences suggest that both a personality and gender perspective should be considered when planning care support aimed at improving adherence and HRQL in people living with asthma and/or allergic rhinitis.IMPLICATIONS FOR PRACTICE: It is suggested that both a personality and gender perspective be taken into account in care support aimed at improving adherence and HRQL in people with asthma and allergic rhinitis.
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11.
  • Axelsson, Malin, 1964, et al. (author)
  • Chronic bronchitis in West Sweden - a matter of smoking and social class
  • 2016
  • In: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 3
  • Journal article (peer-reviewed)abstract
    • Background: Although chronic bronchitis is associated with impaired quality of life, hospitalisations and increased mortality, it has been less in focus after the introduction of the term chronic obstructive pulmonary disease (COPD). There are no recent published data on the prevalence of chronic bronchitis from the Scandinavian countries. Aim: The main aim of the present study was to estimate the prevalence of chronic bronchitis in West Sweden by using data from a large-scale epidemiological study of the general population. A further aim was to identify current risk factors for chronic bronchitis in a population with a major decrease in the proportion of smokers. Methods: From the 18,087 questionnaire responders out of 30,000 invited to participate at the West Sweden Asthma Study, 2,000 subjects were randomly selected and invited to detailed clinical examinations performed during 2009-2013. A total of 1,172 subjects aged 17-79 participated in the examinations which included, among others, spirometry and structured interviews. Chronic bronchitis was defined according to reported symptoms. Results: The overall prevalence of chronic bronchitis was 7.2% (men 7.6%; women 6.8% ns), and it was 8.7% in subjects older than age 60. Chronic bronchitis was strongly associated with smoking, defined both as current smoking status and pack-years. Other risk factors were increasing age, low socio-economic class and urban living. Of those with chronic bronchitis, 22% fulfilled the GOLD criteria of COPD. Conclusion: The prevalence of chronic bronchitis was somewhat lower than found by studies in Sweden in the 1980s and the prevalence was now similar in men and women. Although smoking was still the dominating risk factor for chronic bronchitis, the relative importance of smoking had decreased parallel with a decreasing smoking prevalence, while the relative importance of other factors than smoking had increased compared to previous studies.
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12.
  • Axelsson, Malin, 1964-, et al. (author)
  • Motivational foci and asthma medication tactics directed towards a functional day
  • 2011
  • In: BMC Public Health. - London : BioMed Central. - 1471-2458. ; 11, s. 809-
  • Journal article (peer-reviewed)abstract
    • Background:There appears to be an obvious gap between a medical and patient adherence perspective.Deviating from a medication prescription could be regarded as fairly irrational, but with respect to patients' goals and/or concerns it could be seen as understandable. Thus, the aim was to elucidate adherence reasoning in relation to asthma medication.Methods:This was a qualitative study; data collection and analysis procedures were conducted according to Grounded Theory methodology. Eighteen persons, aged 22 with asthma and regular asthma medication treatment, were interviewed.Results:The emerged theoretical model illustrated that adherence to asthma medication was motivated by three foci, all directed towards a desired outcome in terms of a functional day as desired by the patient. Apromotive focus was associated with the ambition to achieve a positive asthma outcome by being adherent either to the received prescription or to a self-adjusted dosage. A preventive focuswas intended to ensure avoidance of a negative asthma outcome either by sticking to the prescription or by preventively overusing the medication. A permissive focus was associated with unstructured adherence behaviour in which medication intake was primarily triggered by asthma symptoms.Conclusions:As all participants had consciously adopted functioning medication tactics that directed themtowards the desired goal of a functional day. In an effort to bridge the gap between a patient- and a medical adherence perspective, patients need support in defining their desired functionality and guidance in developing a person-based medication tactic.
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13.
  • Axelsson, Malin, 1964-, et al. (author)
  • Personality, adherence, asthma control and health-related quality of life in young adult asthmatics
  • 2009
  • In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 103:7, s. 1033-1040
  • Journal article (peer-reviewed)abstract
    • BackgroundStriving for improved adherence and asthma control is of vital concern in today's asthma management. Several influential factors have been identified, but the importance of personality traits has been insufficiently explored. The aim was first to determine whether personality traits in young adult asthmatics are related to asthma control and health-related quality of life (HRQL), and second to examine the influences of personality traits on adherence to regular asthma medication treatment.MethodsYoung adult asthmatics, 22 years of age (n = 268) completed questionnaires. Statistical analyses were performed.ResultsThe personality traits Negative Affectivity and Impulsivity correlated negatively with asthma control, whereas in women Hedonic Capacity correlated positively with asthma control. Negative Affectivity, Impulsivity, Hedonic Capacity, Alexithymia and asthma control predicted the mental dimension of HRQL. Asthma control and physical activity predicted the physical dimension of HRQL. Among respondents with regular asthma medication (n = 109), Impulsivity correlated negatively with adherence. In men, Antagonism and Alexithymia were associated with low adherence. Additionally, Alexithymia, Hedonic Capacity and Negative Affectivity showed non-linear relationships with adherence, meaning that initially increased scores on these personality traits scales were associated with increased adherence but higher scores did not increase adherence. Respondents who were prescribed a single inhaler combining ICS and LABA reported higher adherence than those with monotherapies.ConclusionThese data suggest that personality can influence how asthma patients adhere to asthma medication treatment, and report their control and HRQL. Tools determining personality traits may be useful in the future in individualizing management of asthma patients.
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14.
  • Axelsson, Malin, et al. (author)
  • Personality and unachieved treatment goals related to poor adherence to asthma medication in a newly developed adherence questionnaire : a population-based study
  • 2016
  • In: Multidisciplinary Respiratory Medicine. - : BioMed Central. - 1828-695X .- 2049-6958. ; 11:42
  • Journal article (peer-reviewed)abstract
    • Background Health-care professionals have a responsibility to be attentive to patients’ adherence behavior but it could be difficult to identify poor adherence in the context of clinical practice. Assessment of personality could be used to identify individuals who are in need for support with their adherence behavior. To our knowledge, existing adherence questionnaires are not based on individuals reflecting asthmatics in the general population and there is limited research describing adherence with asthma medication in relation to personal goals with the treatment. The aim was to develop and validate an adherence questionnaire in adult individuals with asthma from the general population and to assess adherence in relation to personality traits and goals with the asthma medication using the developed questionnaire. Methods The study was conducted in three phases: 1. A preliminary postal 46-item questionnaire was refined after psychometric testing (n = 157). 2. The questionnaire was validated (n = 104). 3. The developed adherence questionnaire was analyzed in relation to personality traits and achieved goals with the asthma medication. Adult respondents with physician diagnosed asthma using asthma medications were selected from the population-based West Sweden Asthma Study. The respondents completed the Neuroticism, Extraversion and Openness to Experience Five-Factor Inventory and the Medication Adherence Report Scale and stated their goals with the asthma medication. Data were analyzed using t-tests, correlations, multiple regression and principal component analysis. Results A final questionnaire was developed consisting of ten items organized in three subscales - “medication routines”, “self-adjusting the medication” and “concerns about side-effects”. Two of the subscales - “medication routines” and “self-adjusting the medication” – were associated with the Medication Adherence Report Scale. The subscale “medication routines” was associated with the personality traits – Conscientiousness and Neuroticism and unachieved goals with the asthma medication. Conclusions The developed questionnaire appears to be useful for measuring adherence to asthma medication in adult individuals with asthma. The study suggests that both individual differences and personal treatment goals need to be addressed in efforts to promote adherence to asthma medication treatment.
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15.
  • Axelsson, Malin, 1964-, et al. (author)
  • Recent educational interventions for improvement of asthma medication adherence.
  • 2012
  • In: Asia Pacific allergy. - Korea : Asia Pacific Association of Allergy, Asthma and Clinical Immunology. - 2233-8276 .- 2233-8268. ; 2:1, s. 67-75
  • Journal article (peer-reviewed)abstract
    • Poor adherence to asthma medication treatment is a dilemma as it decreases the chance of achieving and maintaining a proper asthma control. Another dilemma is that there seems to be a small range of functional interventions that enhance adherence to long-term medication treatments. The aim was to review the last five years of published educational interventions for improving adherence to asthma medication. Through systematic database searches 20 articles were identified, which matched the inclusion criteria and described educational interventions to improve asthma self-management including adherence. The current review showed that addressing unintentional non-adherence in terms of incorrect inhaler technique by recurrent education improved the technique among many patients, but not among all. Phoning patients, as a means to remove medication beliefs as adherence barriers, seemed to be an effective educational strategy, shown as increased adherence. Involving patients in treatment decisions and individualising or tailoring educational support also seemed to have favourable effect on adherence. To conclude, addressing specific adherence barriers such as poor inhaler technique or medication beliefs could favour adherence. To change adherence behavior, the current review proposes that educational adherence support should be a collaborative effort between the patient and the health-care professional based on each individual patient's needs and patient factors, including elements such as personality traits.
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16.
  • Axelsson, Malin, 1964, et al. (author)
  • Self-efficacy and adherence as mediating factors between personality traits and health-related quality of life.
  • 2013
  • In: Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. - : Springer Science and Business Media LLC. - 1573-2649 .- 0962-9343. ; 22:3, s. 567-575
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Personality traits are rather stable dispositions in adulthood, while self-efficacy and adherence may be modified through targeted interventions. Health-related quality of life (HRQL) serves as a vital outcome measure. The present aim was to explore the function of self-efficacy and adherence as mediators for the influencing effect of personality traits on HRQL in people with chronic disease. METHODS: An epidemiological sample of 786 persons completed questionnaires on personality, general self-efficacy, adherence behaviour and HRQL. Data were statistically analysed using descriptive statistics, correlation analyses and path models. RESULTS: Self-efficacy mediated the effect of Extraversion and Conscientiousness on mental HRQL. Neuroticism had a direct effect on both physical and mental HRQL. Adherence partially mediated the effect of both Agreeableness and Conscientiousness on mental HRQL. CONCLUSIONS: The mental HRQL in people scoring low on Extraversion or low on Conscientiousness could be improved by strengthening general self-efficacy. Increasing adherence in people scoring low on Agreeableness or Conscientiousness could improve their mental HRQL, but the improvement was small and may be of lesser clinical relevance. These results argue for personalized interventions intended to positively affect health outcomes in people with chronic disease.
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17.
  • Axelsson, Malin, 1964, et al. (author)
  • The function of medication beliefs as mediators between personality traits and adherence behavior in people with asthma
  • 2013
  • In: Patient Preference and Adherence. - : Informa UK Limited. - 1177-889X. ; 7, s. 1101-1109
  • Journal article (peer-reviewed)abstract
    • Background: There is evidence that both personality traits and personal beliefs about medications affect adherence behavior. However, limited research exists on how personality and beliefs about asthma medication interact in influencing adherence behavior in people with asthma. To extend our knowledge in this area of adherence research, we aimed to determine the mediating effects of beliefs about asthma medication between personality traits and adherence behavior. Methods: Asthmatics (n=516) selected from a population-based study called West Sweden Asthma Study completed the Neuroticism, Extraversion and Openness to Experience Five-Factor Inventory, the Medication Adherence Report Scale, and the Beliefs about Medicines Questionnaire. Data were analyzed using confirmatory factor analysis and structural equation modeling. Results: Three of the five investigated personality traits - agreeableness, conscientiousness, and neuroticism - were associated with both concerns about asthma medication and adherence behavior. Concerns functioned as a partial mediator for the influencing effects of agreeableness, conscientiousness, and neuroticism on adherence behavior. Conclusion: The findings suggest that personality traits could be used to identify individuals with asthma who need support with their adherence behavior. Additionally, targeting concerns about asthma medication in asthmatics with low levels of agreeableness or conscientiousness or high levels of neuroticism could have a favorable effect on their adherence behavior.
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18.
  • Axelsson, Malin, 1964-, et al. (author)
  • The influence of personality traits on reported adherence to medication in individuals with chronic disease : An Epidemiological study in West Sweden
  • 2011
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3
  • Journal article (peer-reviewed)abstract
    • Background: Limited research exists exploring the influence of personality on adherence behaviour. Since non-adherence is a major obstacle in treating prevalent chronic diseases the aim was to determine whether personality traits are related to reported adherence to medication in individuals with chronic disease. Methodology/Principal Findings: Individuals with chronic disease (n = 749) were identified in a random population sample of 5000 inhabitants aged 30-70 in two municipalities in West Sweden. Data on five personality traits, Neuroticism, Extraversion, Openness to experiences, Agreeableness, and Conscientiousness, and medication adherence behaviour was collected by questionnaires. Statistical analyses resulted in a negative relationship between Neuroticism and medication adherence (P<0.001), while both Agreeableness (P<0.001) and Conscientiousness (P<0.001) were positively related to adherence. At high levels of Conscientiousness, low adherence was related to higher scores in Neuroticism. At high levels of Agreeableness, low adherence was related to low scores in Conscientiousness and high scores in Openness to experiences. Conclusions: This study demonstrated that multiple personality traits are of significant importance for adherence behaviour in individuals with chronic disease. The findings suggest that several personality traits may interact in influencing adherence behaviour. Personality traits could putatively be used to focus efforts to educate and support patients with high risk of low medical adherence. © 2011 Axelsson et al.
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19.
  • Babusyte,, et al. (author)
  • Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD.
  • 2007
  • In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-993X. ; 8:1
  • Journal article (peer-reviewed)abstract
    • ABSTRACT: BACKGROUND: Smoking activates and recruits inflammatory cells and proteases to the airways. Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema. However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown. We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago. METHODS: 39 COPD outpatients - smokers (n=22) and ex-smokers (n=17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups. IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis. RESULTS: The number of IS neutrophils was higher in both COPD groups compared to both controls. The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers. The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6+/-0.3x106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9+/-0.4, 0.4+/-0.2, 0.2+/-0.1x106/ml respectively, p<0.05). CONCLUSIONS: The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation. Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients.
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20.
  • Backman, Helena, et al. (author)
  • Decreased COPD prevalence in Sweden after decades of decrease in smoking
  • 2020
  • In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
  • Journal article (peer-reviewed)abstract
    • BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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21.
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22.
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23.
  • Bateman, Eric D, et al. (author)
  • Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial.
  • 2012
  • In: Respiratory medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 106:5, s. 642-50
  • Journal article (peer-reviewed)abstract
    • This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development.
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24.
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25.
  • Bjerg, Anders, 1982, et al. (author)
  • Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
  • 2013
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Background Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds. Results Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years. Discussion In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
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26.
  • Bjerg, Anders, 1982, et al. (author)
  • Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood
  • 2016
  • In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:10, s. 1328-1336
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: To date, most studies of the "allergy epidemic" have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults.OBJECTIVE: To study allergic sensitization, its risk factors, and time trends in prevalence.METHODS: Within West Sweden Asthma Study (WSAS) a population-based sample of 788 adults (17-60y) underwent skin prick tests (SPT) for 11 aeroallergens 2009-2012. Specific IgE was analyzed in 750 of the participants. Those aged 20-46y (n=379) were compared with the European Community Respiratory Health Survey sample aged 20-46y from the same area (n=591) in 1991-1992.RESULTS: Among those aged 20-46y the prevalence of positive SPT to pollen increased; timothy from 17.1% to 29.0% (p<0.001) and birch from 15.6% to 23.7% (p=0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60y any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98) respectively.CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990's, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.
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27.
  • Bjerg, Anders, et al. (author)
  • Increased Prevalence of Symptoms of Rhinitis but Not of Asthma between 1990 and 2008 in Swedish Adults : Comparisons of the ECRHS and GA(2)LEN Surveys
  • 2011
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. e16082-
  • Journal article (peer-reviewed)abstract
    • Background: The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008. Methods: In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA(2)LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umea) and age interval (20-44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed. Results: The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of "asthma-related symptoms" was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased. Conclusion: From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.
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28.
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29.
  • Bjerg, Anders, 1982, et al. (author)
  • The future of combining inhaled drugs for COPD
  • 2012
  • In: Current Opinion in Pharmacology. - : Elsevier BV. - 1471-4892. ; 12:3, s. 252-255
  • Journal article (peer-reviewed)abstract
    • Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality globally, and its prevalence is projected to continue to increase owing to trends in smoking. Treatment of COPD has evolved from the initial adaptations of drugs and treatment strategies successfully used in asthma into more specific pharmacological strategies following global guidelines. Bronchodilating anticholinergic and beta-2-stimulating agents and anti-inflammatory corticosteroid drugs delivered by inhalators are the mainstay of COPD treatment. Despite significant progress, current pharmacotherapies neither fully alleviate the airway obstruction in COPD, nor reverse the progressive nature of the disease. This review discusses inhalation therapies which have recently become clinically available or are being developed, with focus on combination therapies. There is accumulating evidence that the combination of two or all three drug classes, triple therapy, is superior to single drug therapy. Several fixed combinations of both currently available and novel molecules will be launched for clinical use within the next few years. Also, improved understanding of subgroups within the clinical spectrum of COPD, is likely to offer new potentials to improve COPD care.
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30.
  • Bjermer, Leif, et al. (author)
  • Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD
  • 2013
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 107:1, s. 84-90
  • Journal article (peer-reviewed)abstract
    • There is still a need for new agents which improve upon the therapeutic index of tiotropium, the current standard of care for many patients with chronic obstructive pulmonary disease (COPD). We examined in patients with COPD the efficacy of single doses of AZD9164, an M3-selective muscarinic antagonist, to identify an appropriate dose-range for future studies. COPD patients (n = 28) inhaled AZD9164 (100, 400 and 1200 μg), tiotropium (18 μg) and placebo at 5 study centre visits (Clinicaltrials.gov identifier NCT00939211). The effects of these test drugs on average (Eav), peak (Emax) and trough (E22–26) forced expiratory volume in one second (FEV1) were assessed, as were systemically-mediated effects and the safety and exposure of single doses of AZD9164. AZD9164 100, 400 and 1200 μg caused increases in FEV1 to peak effects of 12, 17 and 12% above baseline respectively, following an initial transient and dose-related fall in FEV1 and associated increase in mild respiratory symptoms such as cough. Bronchodilation was maintained overnight, with minimal FEV1 decline. AZD9164 400 and 1200 μg produced larger effects than tiotropium on E22–26 (p < 0.05; both doses) while AZD9164 400 μg also had larger effects on Emax (p = 0.001) and Eav (p < 0.05). There were no serious adverse events and statistically significant systemic effects were observed only with AZD9164 1200 μg. AZD9164 may improve upon the therapeutic index of tiotropium, increasing the magnitude and duration of lung function improvements without increasing systemically-mediated adverse events. The initial bronchoconstrictor effect of AZD9164 requires further investigation.
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31.
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32.
  • Bleecker, E. R., et al. (author)
  • Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids
  • 2012
  • In: Annals of Allergy Asthma & Immunology. - : Elsevier BV. - 1081-1206. ; 109:5
  • Journal article (peer-reviewed)abstract
    • Background: Fluticasone furoate (FF) is an inhaled corticosteroid (ICS) with 24-hour activity in development as a once-daily treatment for the long-term management of asthma. Objective: To assess the efficacy and safety of 4 doses of once-daily FF administered using a dry powder inhaler in patients (>12 years) with moderate asthma, uncontrolled on low-dose ICS (fluticasone propionate [FP] 200 mu g/day or equivalent). Methods: This double-blind, placebo-controlled, dose-ranging study randomized 622 patients to 1 of 6 treatments: FF (100, 200, 300, or 400 mu g) once daily in the evening, FP 250 mu g twice daily (active control), or placebo for 8 weeks. The primary endpoint was the change from baseline in predose evening forced expiratory colume in 1 second (FEV1) at week 8. Results: At week 8, relative to placebo, all doses of FF once daily and FP twice daily demonstrated significantly (P < .001) greater increases from baseline and greater than 200-mL increases in predose FEV1. There was no evidence of a dose-response relationship between FF doses. Improvement with once-daily FF was similar to or greater than that for twice-daily FP. Secondary efficacy endpoint findings generally supported the efficacy of FF 100 to 400 mu g once daily, although statistically significant improvements versus placebo in symptom-free 24-hour periods were only reported for FF 400 mu g. There were few withdrawals due to lack of efficacy. Oral candidiasis was reported in 0 to 4% of patients; 24-hour urinary cortisol excretion ratios were similar across active treatment groups and not significantly different from placebo. Conclusion: FF 100 to 400 mu g once daily in the evening is effective and well tolerated in patients with asthma uncontrolled on low-dose ICS, with 100 mu g and 200 mu g, considered the most applicable doses in this asthma population. Trial Registration: clinicaltrials.gov Identifier: NCT00603278. (C) 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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33.
  • Bonini, S., et al. (author)
  • Allergy and clinical immunology services in europe*
  • 2006
  • In: Allergy.. ; 61:10
  • Journal article (peer-reviewed)abstract
    • Allergology and Clinical Immunology (ACI) is an area of clinical medicine with a precise identity, relevant recent scientific achievements and well-defined educational and professional needs. In spite of the high individual and socio-economic impact of allergic diseases in Europe, the organization of ACI services is imperfect and varies among countries according to their health policies and priorities. In the firm belief of the role of ACI specialists in addressing clinical issues related to the involvement of the immune system in health and diseases-such as vaccination, immunodeficiencies, susceptibility and response to microbial agents, autoimmune and allergic diseases, immune aspects of transplantation and malignancies, in vivo and in vitro immunological tests, vaccinations, immuno-modifiers-the European Academy of Allergology and Clinical Immunology appointed an ad hoc Task Force to produce standards for ACI Services in Europe. The resulting position paper should be used as a consulting reference for National Health Services as a necessary pre-requisite for the free circulation to patients and health care professionals.
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34.
  • Bossios, Apostolos, 1969, et al. (author)
  • IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.
  • 2009
  • In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; :Nov 26
  • Journal article (peer-reviewed)abstract
    • To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome. Allergy 2009. DOI: 10.1111/j.1398-9995.2009.02271.x.Abstract Background: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. Methods: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. Results: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. Conclusion: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
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35.
  • Bossios, Apostolos, 1969, et al. (author)
  • Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.
  • 2008
  • In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 38:10, s. 1615-26
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. OBJECTIVE: To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. METHODS: BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. RESULTS: RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. CONCLUSION: HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.
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36.
  • Bousquet, Jean, et al. (author)
  • Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper.
  • 2010
  • In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:10, s. 1212-21
  • Journal article (peer-reviewed)abstract
    • The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
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37.
  • Bousquet, J, et al. (author)
  • GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma 'epidemic'.
  • 2009
  • In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:7, s. 969-77
  • Journal article (peer-reviewed)abstract
    • Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA(2)LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan-European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA(2)LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project-related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA(2)LEN are reported in this paper.
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38.
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39.
  • Busse, WW, et al. (author)
  • Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial
  • 2012
  • In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 67:1, s. 35-41
  • Journal article (peer-reviewed)abstract
    • Abstract Background Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β(2) agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease. Objectives To determine the optimal dose(s) of FF for treating patients with asthma. Methods An 8-week multicentre, randomised, double-blind study. 627 patients with persistent moderate-to-severe asthma, symptomatic on medium-dose inhaled corticosteroid therapy, were randomised to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a novel dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus™/Accuhaler™). The primary efficacy measure was mean change from baseline in pre-dose evening forced expiratory volume in one second (FEV(1)). Other endpoints included morning and evening peak expiratory flow, and rescue/symptom-free 24 h periods. Results Each dose was significantly superior to placebo for the primary endpoint (p<0.001) with efficacy at least similar to that reported with fluticasone propionate. There was no dose-response relationship across the FF doses studied. Peak expiratory flow improved in all groups (p<0.001 vs placebo), and there were significant treatment effects on rescue/symptom-free 24 h periods with all active treatments. FF was generally well tolerated. The incidence of oral candidiasis was higher with FF 800 μg than placebo; pharmacokinetic and 24 h urinary cortisol analyses confirmed a higher systemic exposure of FF at this highest dose level. Conclusions FF doses <800 μg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 μg is an appropriate dose in patients with moderate persistent asthma. ClinicalTrials.gov identifier NCT00603746
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40.
  • Busse, W. W., et al. (author)
  • Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial
  • 2014
  • In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:11, s. 1522-1530
  • Journal article (peer-reviewed)abstract
    • Background: Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50 mcg in patients with mild-tomoderate persistent asthma. Methods: A 24-week, multicenter, randomized, placebo-controlled and active-controlled, double-blind, double-dummy, parallel-group phase III study. Three hundred and fifty-one patients (aged >= 12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1 : 1 : 1) with once-daily FF 50 mcg dosed in the evening, twice-daily fluticasone propionate (FP) 100 mcg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1 s (FEVI) at Week 24. Secondary endpoints were change from baseline in the percentage of rescue-free 24-h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24-h periods and number of withdrawals due to lack of efficacy. Results: Evening trough FEYI at Week 24 was not statistically significantly increased with FF 50 mcg once-daily (37 ml [95% CI: 55, 128]; P = 0.430), but was with FP 100 mcg twice daily (102 ml [10, 194]; P = 0.030), vs placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment. Conclusions: FP 100 mcg twice daily improved evening trough FEVI in patients with mild-to-moderate persistent asthma, but FF 50 mcg once daily did not demonstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP.
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41.
  • Busse, W. W., et al. (author)
  • Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the beta(2) agonist vilanterol administered once daily for 52 weeks in patients >= 12 years old with asthma: a randomised trial
  • 2013
  • In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 68:6, s. 513-520
  • Journal article (peer-reviewed)abstract
    • Background The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease. Objective To assess the safety and tolerability of FF/VI over 52weeks in patients with asthma. Methods Patients (aged ≥12years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25µg or FF/VI 200/25µg once daily in the evening, or fluticasone propionate (FP) 500µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate. Results On-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25µg and 1.09 [0.87 to 1.38] for FF/VI 200/25µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25µg]; 3.4bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1bpm FF/VI vs 5bpm FP; Week 52). Conclusions FF/VI (100/25µg or 200/25µg) administered once daily over 52weeks was well tolerated by patients aged ≥12years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.
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42.
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43.
  • Calderon, Moises A, et al. (author)
  • EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
  • 2012
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
  • Journal article (peer-reviewed)abstract
    • Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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44.
  • Cazzola, M., et al. (author)
  • Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: A randomized, placebo-controlled, double-blind, crossover study
  • 2012
  • In: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 32:3, s. 147-155
  • Journal article (peer-reviewed)abstract
    • Background: Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD. Objective: This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD. Methods: In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV 1) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12%increase in FEV1 at 5 minutes post-dose. Results: 109 patients were randomized, and 108 completed the study. The increase in FEV1 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV 1 5 minutes post-dose were 23.1%, 9.2%and 6.4%for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated. Conclusion: In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV 1 at 5minutes post-dose. © 2012 Adis Data Information BV. All rights reserved.
  •  
45.
  • Cazzola, Mario, et al. (author)
  • Ultra long-acting beta2-agonists in development for asthma and chronic obstructive pulmonary disease
  • 2005
  • In: Expert Opin Investig Drugs. ; 14:7
  • Journal article (peer-reviewed)abstract
    • After the discovery of formoterol and salmeterol, new candidates for long-acting beta2-adrenoceptor agonists (LABAs) have emerged from various companies. In particular, once-daily beta2-adrenoceptor agonists such as arformoterol, carmoterol, indacaterol, GSK-159797, GSK-597901, 159802, 642444 and 678007 are under development for the treatment of asthma and chronic obstructive pulmonary disease. The majority of these compounds are (R,R)-isomers in order to control desensitisation and accumulation. Several options for combination products are currently being evaluated in parallel with the development of these ultra LABAs. Once-daily dosing of an ultra LABA would be a significant convenience and probably a compliance-enhancing advantage leading to improved overall clinical outcomes in patients with asthma and chronic obstructive pulmonary disease. The only limits set for the development of a LABA with a new product profile are medical needs and marketing opportunities.
  •  
46.
  • Cheung, K. H., et al. (author)
  • Extending gene ontology in the context of extracellular RNA and vesicle communication
  • 2016
  • In: Journal of Biomedical Semantics. - : Springer Science and Business Media LLC. - 2041-1480. ; 7
  • Journal article (peer-reviewed)abstract
    • Background: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. Methods: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. Results: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. Conclusions: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
  •  
47.
  • Couch, Y., et al. (author)
  • A brief history of nearly EV-erything - The rise and rise of extracellular vesicles
  • 2021
  • In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 10:14
  • Journal article (peer-reviewed)abstract
    • Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.
  •  
48.
  • Crescitelli, Rossella, 1985, et al. (author)
  • Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes.
  • 2013
  • In: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 2
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: In recent years, there has been an exponential increase in the number of studies aiming to understand the biology of exosomes, as well as other extracellular vesicles. However, classification of membrane vesicles and the appropriate protocols for their isolation are still under intense discussion and investigation. When isolating vesicles, it is crucial to use systems that are able to separate them, to avoid cross-contamination. METHOD: EVS RELEASED FROM THREE DIFFERENT KINDS OF CELL LINES: HMC-1, TF-1 and BV-2 were isolated using two centrifugation-based protocols. In protocol 1, apoptotic bodies were collected at 2,000×g, followed by filtering the supernatant through 0.8 µm pores and pelleting of microvesicles at 12,200×g. In protocol 2, apoptotic bodies and microvesicles were collected together at 16,500×g, followed by filtering of the supernatant through 0.2 µm pores and pelleting of exosomes at 120,000×g. Extracellular vesicles were analyzed by transmission electron microscopy, flow cytometry and the RNA profiles were investigated using a Bioanalyzer(®). RESULTS: RNA profiles showed that ribosomal RNA was primary detectable in apoptotic bodies and smaller RNAs without prominent ribosomal RNA peaks in exosomes. In contrast, microvesicles contained little or no RNA except for microvesicles collected from TF-1 cell cultures. The different vesicle pellets showed highly different distribution of size, shape and electron density with typical apoptotic body, microvesicle and exosome characteristics when analyzed by transmission electron microscopy. Flow cytometry revealed the presence of CD63 and CD81 in all vesicles investigated, as well as CD9 except in the TF-1-derived vesicles, as these cells do not express CD9. CONCLUSIONS: Our results demonstrate that centrifugation-based protocols are simple and fast systems to distinguish subpopulations of extracellular vesicles. Different vesicles show different RNA profiles and morphological characteristics, but they are indistinguishable using CD63-coated beads for flow cytometry analysis.
  •  
49.
  • Crescitelli, Rossella, 1985, et al. (author)
  • Extracellular vesicle DNA from human melanoma tissues contains cancer-specific mutations
  • 2022
  • In: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 10
  • Journal article (peer-reviewed)abstract
    • Liquid biopsies are promising tools for early diagnosis and residual disease monitoring in patients with cancer, and circulating tumor DNA isolated from plasma has been extensively studied as it has been shown to contain tumor-specific mutations. Extracellular vesicles (EVs) present in tumor tissues carry tumor-derived molecules such as proteins and nucleic acids, and thus EVs can potentially represent a source of cancer-specific DNA. Here we identified the presence of tumor-specific DNA mutations in EVs isolated from six human melanoma metastatic tissues and compared the results with tumor tissue DNA and plasma DNA. Tumor tissue EVs were isolated using enzymatic treatment followed by ultracentrifugation and iodixanol density cushion isolation. A panel of 34 melanoma-related genes was investigated using ultra-sensitive sequencing (SiMSen-seq). We detected mutations in six genes in the EVs (BRAF, NRAS, CDKN2A, STK19, PPP6C, and RAC), and at least one mutation was detected in all melanoma EV samples. Interestingly, the mutant allele frequency was higher in DNA isolated from tumor-derived EVs compared to total DNA extracted directly from plasma DNA, supporting the potential role of tumor EVs as future biomarkers in melanoma.
  •  
50.
  • Crescitelli, Rossella, 1985, et al. (author)
  • Isolation and characterization of extracellular vesicle subpopulations from tissues.
  • 2021
  • In: Nature protocols. - : Springer Science and Business Media LLC. - 1750-2799 .- 1754-2189. ; 16, s. 1548-1580
  • Journal article (peer-reviewed)abstract
    • Extracellular vesicles (EVs) are lipid bilayered membrane structures released by all cells. Most EV studies have been performed by using cell lines or body fluids, but the number of studies on tissue-derived EVs is still limited. Here, we present a protocol to isolate up to six different EV subpopulations directly from tissues. The approach includes enzymatic treatment of dissociated tissues followed by differential ultracentrifugation and density separation. The isolated EV subpopulations are characterized by electron microscopy and RNA profiling. In addition, their protein cargo can be determined with mass spectrometry, western blot and ExoView. Tissue-EV isolation can be performed in 22 h, but a simplified version can be completed in 8 h. Most experiments with the protocol have used human melanoma metastases, but the protocol can be applied to other cancer and non-cancer tissues. The procedure can be adopted by researchers experienced with cell culture and EV isolation.
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