| 1. |
- Striz, Ilja, et al.
(författare)
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New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis
- 2023
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Ingår i: Clinical Science. - 0143-5221. ; 137:9, s. 727-753
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Forskningsöversikt (refereegranskat)abstract
- Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.
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| 2. |
- Abd-Elaziz, Khalid, et al.
(författare)
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First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025 : Results from Two Randomized Studies in Healthy Subjects
- 2021
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:1, s. 65-76
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects. Methods: Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50–800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation. Results: Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t1/2) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability. Conclusion: FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted. Trial registration number: www.clinicaltrials.gov: NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017.
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| 3. |
- Abd-Elaziz, Khalid, et al.
(författare)
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Revisiting matrix metalloproteinase 12 : its role in pathophysiology of asthma and related pulmonary diseases
- 2021
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Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 27:1, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019. RECENT FINDINGS: In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce. SUMMARY: Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.
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| 4. |
- Agache, Ioana, et al.
(författare)
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Prioritizing research challenges and funding for allergy and asthma and the need for translational research—The European Strategic Forum on Allergic Diseases
- 2019
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:11, s. 2064-2076
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Tidskriftsartikel (refereegranskat)abstract
- The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.
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| 5. |
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| 6. |
- Andersson, Cecilia, et al.
(författare)
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Revisiting the role of the mast cell in asthma.
- 2016
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Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 22:1, s. 10-17
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Forskningsöversikt (refereegranskat)abstract
- In humans, mast cells are ubiquitously present in tissues adjacent to external environment and consequently have an important sentential role in host defence, homeostasis and repair. Their key role in allergen-mediated conditions has been recognized for many decades already. So far, therapies targeting mast cells offered clinical efficacy in allergic conditions except for asthma. More recently, sophisticated sampling and detection techniques revealed pleiotrophic immunological and functional properties of mast cells in and beyond asthma with potential clinical and management implications. These findings bring back the mast cell as a key player in the field of asthma and warrant a review of the recent literature.
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| 7. |
- Assaf, Sara, et al.
(författare)
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Asthma in the era of COVID-19
- 2023
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Ingår i: Respiratory Medicine. - 0954-6111. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Since its global invasion in 2019, COVID-19 has affected several aspects of patients’ lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.
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| 8. |
- Assaf, Sara M., et al.
(författare)
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Asthma and severe acute respiratory syndrome coronavirus 2019 : current evidence and knowledge gaps
- 2021
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Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 27:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Although respiratory viruses are common triggers of asthma exacerbation, it is unknown whether this also applies to infection with SARS-CoV-2. Indeed, patients with asthma and allergy appear underrepresented in large reports of COVID-19 cases worldwide. In this review, we evaluate existing literature on this topic and potential underlying mechanisms for any interrelationship between asthma and COVID-19. RECENT FINDINGS: Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. In addition, some studies suggest that the reported improvement in asthma control and a reduction in asthma exacerbations during the COVID-19 pandemic may be related to improvement in adherence to controller therapy and reduced exposure to triggers, such as other respiratory viruses and air pollutants. Recent data point towards differential susceptibility for COVID-19 among asthma patients based on their phenotype and/or endotype. On the basis of existing evidence, continuation with controller therapies is recommended for all patients with asthma. For patients with severe uncontrolled asthma infected by SARS-CoV-2, adjustment of controllers and biologics should be based on a multidisciplinary decision. SUMMARY: Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications. Although it is imperative that control should be maintained and asthma medications be continued in all patients, management of patients with severe uncontrolled asthma infected by SARS-CoV-2 including adjustment of controllers and biologics should be discussed on an individual basis.
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| 9. |
- Baiardini, Ilaria, et al.
(författare)
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Patient knowledge, perceptions, expectations and satisfaction on allergen-specific immunotherapy: A survey
- 2013
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 107:3, s. 361-367
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessing patient's perspective provides useful information enabling a customized approach which has been advocated by current guidelines. In this multicentre cross-sectional study we evaluated personal viewpoints on allergen-specific immunotherapy (SIT) in patients treated with subcutaneous (SCIT) or sublingual (SLIT) immunotherapy. Methods: A survey of 28 questions assessing patient's knowledge, perceptions, expectations and satisfaction was developed by an expert panel and was applied by physicians from allergology centres in patients with respiratory allergy treated with SIT. Treating physicians independently reported their satisfaction level regarding SIT for each patient. Results: Fully completed surveys from 434 patients (55.3% mate; 66.7% poly-sensitized, 74% SLIT) were analysed. Mean duration of SIT was 2.5 years with different allergens. Most patients acquired their SIT knowledge from their physician (95%) and consequently, their physicians' opinion in their choice to start with SIT was important. Most patients perceived SIT to be safe and easy to integrate into their daily routine. The main motivations for SIT were its supposed potential to alter the course of the disease (45.7%), less need of (28.2%), or dissatisfaction with current pharmacotherapy (19.3%). Both patients' and physicians' satisfaction was high (VAS-scores 74/100 and 78/100, respectively) and showed a significant correlation (SCIT: r = 0.612; SLIT: r = 0.608). No major difference was found in patients' answers based on the level of education. Conclusion: In this real life study evaluating different aspects of patient's perspective on SIT, the majority of patients had an adequate level of knowledge, perceptions, expectations and satisfaction about SIT, which corresponded well with the physician's perceptions and satisfaction. Our data warrant the use of patient's perspectives on chronic SIT treatment. (C) 2012 Elsevier Ltd. All rights reserved.
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| 10. |
- Bjermer, Leif, et al.
(författare)
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Complementary therapy in asthma: inhaled corticosteroids and what?
- 2009
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Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 15:1, s. 46-51
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: For optimal asthma control, complementary strategies are advocated to cover several aspects of the disease. This mini-review highlights different complementary strategies with special focus on the combined use of inhaled corticosteroids (ICSs) and long-acting beta2 agonists and as an alternative, the combination of ICSs and antileukotrienes. RECENT FINDINGS: New data show that combinations of ICSs/long-acting beta2 agonists or ICSs with antileukotrienes improve disease stability with concomitant control of the underlying airway inflammation. Moreover, there is some evidence that combination therapy may prevent some aspects of airway remodelling. The use of a fixed combination of both a reliever and a controller medication may have certain advantages compared with a fixed dose regime with as-needed separate reliever therapy. Alternatively, in some asthma phenotypes, such as combined allergic rhinitis and asthma syndrome, the combination of ICSs with antileukotrienes offers a complementary anti-inflammatory treatment in combination with controller effects on both airway compartments. SUMMARY: This review compares different strategies of complementary therapy in asthma with special focus on how to achieve the best clinical control also aimed at controlling the underlying airway inflammation. We have chosen to focus on two major topics: the use of ICSs and long-acting beta2 agonists in two different strategies, that is, a symptom-driven versus a fixed symptom-preventive approach; and the use of ICSs with a long-acting beta2 agonist versus ICSs and a leukotriene receptor antagonist. What regime should be chosen is highly dependent on the individual phenotype and defined treatment goal.
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