New topics in bradykinin research Maurer, M.; Bader, M.; Bas, M. ...
Allergy (Copenhagen),
November 2011, Letnik:
66, Številka:
11
Journal Article
Recenzirano
Odprti dostop
To cite this article: Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, Howarth P, Kaplan A, Kojda G, Leeb‐Lundberg F, Lötvall J, Magerl M. New topics in bradykinin research. Allergy 2011; 66: ...1397–1406.
Bradykinin has been implicated to contribute to allergic inflammation and the pathogenesis of allergic conditions. It binds to endothelial B1 and B2 receptors and exerts potent pharmacological and physiological effects, notably, decreased blood pressure, increased vascular permeability and the promotion of classical symptoms of inflammation such as vasodilation, hyperthermia, oedema and pain. Towards potential clinical benefit, bradykinin has also been shown to exert potent antithrombogenic, antiproliferative and antifibrogenic effects. The development of pharmacologically active substances, such as bradykinin receptor blockers, opens up new therapeutic options that require further research into bradykinin. This review presents current understanding surrounding the role of bradykinin in nonallergic angioedema and other conditions seen by allergists and emergency physicians, and its potential role as a therapeutic target.
Summary
Background
MicroRNAs (miRNAs) may facilitate cell‐to‐cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear.
...Methods
Airway‐secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house‐dust mite (HDM) allergen‐exposed HDM‐sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray.
Results
The amount of AEV increased 8.9‐fold in BALF from HDM‐exposed mice compared with that from sham‐control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL‐13 and IL‐5Ra, are putative targets of the miRNAs up‐regulated in AEVs but down‐regulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa.
Conclusion
These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation.
Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in ...childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.
Summary
Background In contrast to asthma and rhinitis, few studies among adults investigating the prevalence and risk factors of eczema have been published.
Objectives To investigate the prevalence ...and risk factors of eczema among adults in West Sweden. A further aim was to study the associations between asthma, rhinitis and eczema.
Methods A questionnaire on respiratory health was mailed in 2008 to 30 000 randomly selected subjects in West Sweden aged 16–75 years; 62% responded. The questionnaire included questions about eczema, respiratory symptoms and diseases and their possible determinants. A subgroup of 669 subjects underwent skin prick testing against common airborne allergens.
Results ‘Eczema ever’ was reported by 40·7% and ‘current eczema’ by 11·5%. Both conditions were significantly more common among women. The prevalence decreased with increasing age. The coexistence of both asthma and rhinitis with eczema was common. The main risk factors were family history of allergy and asthma. The dominant environmental risk factor was occupational exposure to gas, dust or fumes. Smoking increased the risk. Eczema was associated with urbanization, while growing up on a farm was associated with a decreased risk. Added one by one to the multivariate model, asthma, allergic rhinitis and any positive skin prick test were associated with eczema.
Conclusions Eczema among adults is a common disease with more women than men having and having had eczema. Eczema is associated with other atopic diseases and with airway symptoms. Hereditary factors and exposure to gas, dust and fumes are associated with eczema.
Summary
Background
Patients with severe asthma are often inadequately controlled on existing anti‐asthma therapy, constituting an unmet clinical need.
Objective
This randomized, double‐blind, ...placebo‐controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti‐IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.
Methods
After a run‐in period when an optimized fluticasone dose (1000 μg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126 or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16‐week add‐on phase of treatment followed by a 16‐week fluticasone‐reduction phase. Short‐/long‐acting β2‐agonists were allowed as needed.
Results
Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 50% dose reduction (P=0.001). Fluticasone dose reduction to 500 μg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo‐treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma‐related quality of life compared to placebo.
Conclusion
Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
Summary
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 (17–60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009–2012. Specific IgE was analysed in 750 of the participants. Those aged 20–46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20–46 year from the same area (n = 591) in 1991–1992.
Results
Among those aged 20–46 years, 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 17–60 years, 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 1990s, 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.
Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, ...bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling. Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined. Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma. OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.
Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric ...asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re‐evaluate and fine‐tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype‐specific treatment choices; however, this goal has not yet been achieved.
Summary Background Striving 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. Methods Young adult asthmatics, 22 years of age ( n = 268) completed questionnaires. Statistical analyses were performed. Results The 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. Conclusion These 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.
To cite this article: Eriksson J, Ekerljung L, Lötvall J, Pullerits T, Wennergren G, Rönmark E, Torén K, Lundbäck B. Growing up on a farm leads to lifelong protection against allergic rhinitis. ...Allergy 2010; 65: 1397-1403. Various studies have reported a low prevalence of allergic rhinitis in farmers and farmers' children. We sought to investigate whether the protective effect of childhood farm environment is conserved throughout adulthood and how it corresponds to different degrees of urbanization. A questionnaire on respiratory health was mailed in 2008 to 30 000 randomly selected subjects aged 16-75 in West Sweden, 29 218 could be traced and 18 087 (62%) responded. The questionnaire included questions on allergic rhinitis, asthma, respiratory symptoms and possible determinants. When stratified into age groups of 15 years, subjects that lived on a farm during their first 5 years of life had a lower prevalence of allergic rhinitis in all groups, even among the oldest (61-75 years). The negative correlation between childhood farm living and prevalence of allergic rhinitis was similar in 46-75 years of age (OR 0.82; 95% CI 0.70-0.95) as in 16-45 years of age (OR 0.78; 0.64-0.95). There was a significant trend of increasing prevalence of allergic rhinitis with increasing degree of urbanization independent of the effect of childhood farm living. We found a lifelong protective effect of childhood farm living on the prevalence of allergic rhinitis. In addition, we found an increasing prevalence of allergic rhinitis with increasing degree of urbanization both in those raised on a farm and those not, thus emphasizing the influence of both childhood and adult exposure for the development of allergic disease.
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