| 1. |
- Bisgaard, H, et al.
(författare)
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Determinants of lung function and airway hyperresponsiveness in asthmatic children
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:7, s. 1477-1482
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAsthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment.MethodsWe analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA).ResultsThe primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV1 percent predicted (FEV1% pred) was 0.25% lower per year of delay from diagnosis until treatment (p=0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking.In the secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV1% pred was inversely related to having asthmatic siblings (−7.9%; p<0.0001), asthma diagnosis (−2.7%; p=0.0007), smoking (−3.5%; p=0.0027), and positive allergy skin prick test (−0.47% per test; p=0.012), while positively related to being of female gender (1.8%; p=0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; p<0.0001).ConclusionsThese data suggest that lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma.
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| 2. |
- Andersson, Emelie, et al.
(författare)
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Disease burden and unmet need for acute allergic reactions - A patient perspective
- 2024
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Ingår i: World Allergy Organization Journal. - : Elsevier. - 1939-4551. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute allergic reactions (AARs) occur shortly after exposure to an allergen, and the severity is on a continuum. Systemic corticosteroids (CS) are mainstay treatment of moderate to severe AARs, whereas those at risk of the most severe AARs (ie, anaphylaxis) are also recommended prescription of epinephrine autoinjectors. There is limited research on the impact of AARs not fulfilling the criteria for anaphylaxis. We have characterized a sample with a history of moderate to severe AARs and evaluated their self-reported disease burden (ie, daily life impact, anxiety, and treatment impediments).Methods: Survey study of adults with experience of AARs treated with CS. Participants recruited from a web-based panel and using social media were asked to complete a questionnaire related to their allergy and experience of AARs. The results were summarized for the whole sample and across subgroups with and without prescription of epinephrine.Results: The final study sample included 387 participants (80% women, mean age 41), of which 129 (33%) had at some point been prescribed epinephrine. The most common symptoms were respiratory (80%) and skin (78%) manifestations, and the mean (standard deviation, SD) self-rated severity score (scale from 0 [very mild] to 10 [very severe]) of the most recent AAR was 6.1 (2.0). More than 80% had experience of AARs interrupting daily activities and 50% of AARs that had limited work/studies or participation in leisure activities. Most of the respondents reported some degree of anxiety related to AARs and 43% had feared for their lives. Moreover, difficulties swallowing allergy medicine at an AAR was experienced by 26% and not having the medicine available when needed by 66%. Participants with prescription of epinephrine experienced more severe AARs than those without such prescription (mean [SD] severity 6.8 [2.1] vs 5.8 [1.8], p < 0.0001); however, also those without epinephrine prescription reported considerable anxiety and impact on daily life and to a similar degree as those with prescription.Conclusions: In this sample, subjects with experience of AARs treated with CS showed a considerable disease burden with anxiety and interruption on daily life, as well as problems related to access to, and swallowing of, medication. Although respondents with epinephrine prescription had more severe disease, a high disease burden was also evident among those without epinephrine. The study increases the knowledge of people with moderate to severe AARs, a patient population that has previously been underrepresented in the research literature.
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| 3. |
- Kasetty, Gopinath, et al.
(författare)
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Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation
- 2019
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:4, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1+/+) and OPN knockout (Spp1−/−) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1−/− mice than in Spp1+/+ mice. Moreover, OPN-deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1+/+ mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1−/− mice. Furthermore, Spp1−/− mice had higher levels of cytokines and immune cells in BALF than did Spp1+/+ mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma.
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| 4. |
- Bjermer, Leif, et al.
(författare)
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Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD : FLAME-based modelling in a Swedish population
- 2017
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. Methods: A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed. Results: IND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers. Conclusion: IND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year.
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| 5. |
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| 6. |
- Bjermer, Leif
(författare)
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Astma är en systemisk inflammation--inte en lokal sjukdom Bred antiinflammatorisk behandlingsstrategi krävs.
- 2009
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Ingår i: Läkartidningen. - 0023-7205. ; 106:30-31, s. 1905-1908
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Forskningsöversikt (refereegranskat)abstract
- The traditional view of asthma has changed considerably during the last decades. A paradigm shift in our understanding of asthma has turned our focus from the importance of muscle spasm to inflammation. Today asthma is believed to be a central airway inflammatory disorder, and the importance of activated eosinophils found in central airway biopsies and in induced sputum is believed to be a hallmark of this inflammatory process. Anti-inflammatory treatment in asthma has for long been seen as treatment with cortisone. Moreover, the view of asthma as mainly a central airway disorder, make it logic to treat this what is believed to be a central airway disorder, locally by the inhaled route. During the recent year we have gained a lot of new knowledge challenging the current view of asthma. While previous asthma treatment guidelines mainly have focused on asthma as a organ disorder, more modern guidelines such as ARIA (Allergic Rhinitis and its Impact on Asthma) have revealed the necessity of treating not only the lower but also the upper airways. It is also clear that corticosteroid therapy do not suppress all parts of the asthmatic inflammation and other, more or less “steroid refractory mechanisms” ask for complementary strategies in order to achieve a better control of the asthmatic inflammation. Finally, not only the upper airways seem to be commonly involved in asthma patients. The peripheral “small airways” and the lung parenchyma, as well as organs outside the thorax, contribute to the inflammatory burden of the disease. Thus in order to be able to advance further in our management strategies we need to change our view of asthma from an organ centred to a more systemic approach. It is really time for a paradigm shift!
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| 7. |
- Dahl, Ronald, et al.
(författare)
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Nordic consensus report on asthma management. Nordic Asthma Consensus Group.
- 2000
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Ingår i: Respiratory medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 94:4, s. 299-327
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Forskningsöversikt (refereegranskat)abstract
- The work with the Nordic consensus report on asthma management started some years ago. The Nordic countries have common socioeconomic conditions. We acknowledge the international as well as other European guidelines providing valuable recommendations. Nevertheless, we felt the need to combine the common Nordic experiences in order to have a local statement of asthma and asthma care, based upon Nordic clinical science and tradition. The work has been rewarding and we acknowledge many valuable contributions from paediatricians, allergologists and lung physicians in all Nordic countries. The response has so far been positive and we feel that the present material reflects the main opinion of Nordic physicians taking care of asthma patients of all ages. However, the asthma and allergy research field is rapidly developing. Thus, this document should merely be regarded as a time-limited contribution to the continuing scientific discussion of this fascinating field.
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| 8. |
- Abdillahi, Suado M, et al.
(författare)
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The Pulmonary Extracellular Matrix Is a Bactericidal Barrier Against Haemophilus influenzae in Chronic Obstructive Pulmonary Disease (COPD) : Implications for an in vivo Innate Host Defense Function of Collagen VI
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human commensal commonly residing in the nasopharynx of preschool children. It occasionally causes upper respiratory tract infection such as acute otitis media, but can also spread to the lower respiratory tract causing bronchitis and pneumonia. There is increasing recognition that NTHi has an important role in chronic lower respiratory tract inflammation, particularly in persistent infection in patients suffering from chronic obstructive pulmonary disease (COPD). Here, we set out to assess the innate protective effects of collagen VI, a ubiquitous extracellular matrix component, against NTHi infection in vivo. In vitro, collagen VI rapidly kills bacteria through pore formation and membrane rupture, followed by exudation of intracellular content. This effect is mediated by specific binding of the von Willebrand A (VWA) domains of collagen VI to the NTHi surface adhesins protein E (PE) and Haemophilus autotransporter protein (Hap). Similar observations were made in vivo specimens from murine airways and COPD patient biopsies. NTHi bacteria adhered to collagen fibrils in the airway mucosa and were rapidly killed by membrane destabilization. The significance in host-pathogen interplay of one of these molecules, PE, was highlighted by the observation that it confers partial protection from bacterial killing. Bacteria lacking PE were more prone to antimicrobial activity than NTHi expressing PE. Altogether the data shed new light on the carefully orchestrated molecular events of the host-pathogen interplay in COPD and emphasize the importance of the extracellular matrix as a novel branch of innate host defense.
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| 9. |
- Roth-Walter, Franziska, et al.
(författare)
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Immune modulation via T regulatory cell enhancement : Disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases—An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)
- 2021
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 76:1, s. 90-113
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell–based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell–based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell–based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.
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| 10. |
- Scadding, Glenis K., et al.
(författare)
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Allergic respiratory disease care in the COVID-19 era : A EUFOREA statement
- 2020
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Ingår i: World Allergy Organization Journal. - : Elsevier BV. - 1939-4551. ; 13:5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Spring and Summer 2020 are unique in that the challenges of care for those suffering from pollen allergy coincide with the COVID-19 pandemic. Several considerations are important to allow optimal care of allergic rhinitis (AR) and asthma and hence prevention of coronavirus spread through sneezing, rhinorrhoea, and coughing. This compact overview of recommendations by the EUFOREA expert teams on allergic airway diseases and allergen-specific immunotherapy (AIT) is based on investigation of the current COVID-19 literature in association with the key words above and shared clinical experience of the experts involved. It deals with similarities and differences between AR and coronavirus infection, specific recommendations for allergic disease care in the COVID-19 era, including guidance on AIT.
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