Publications by authors named "Kirsten A"

Article Synopsis
  • COPD is a chronic inflammatory lung disease, and there's a need for new anti-inflammatory treatments, particularly those targeting the PI3K pathway, with CHF6523 being an inhaled PI3Kδ inhibitor showing promise in preliminary tests.
  • The study involved 44 patients with stable COPD, using a randomized double-blind design with two treatment phases over 28 days each, to evaluate the safety, tolerability, and pharmacokinetics of CHF6523 compared to a placebo.
  • Results indicated that CHF6523 effectively reduced a key inflammatory marker (PIP) by 29.7% from baseline, with pharmacokinetic data suggesting limited drug accumulation and quick absorption after inhalation.
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Background: The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD.

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Article Synopsis
  • Researchers aimed to validate the Late-Life Function and Disability Instrument (LLFDI) for assessing disability and loss of function specifically in people with Chronic Obstructive Pulmonary Disease (COPD).
  • The study involved 605 COPD patients from six European countries, analyzing LLFDI scores and their correlations with physical functioning, symptoms, and health status.
  • Results showed moderate validation of the LLFDI across various domains, highlighting significant correlations with disease severity and functional limitations but suggesting adjustments for some subdomains.
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The question whether interference with the ubiquitous splicing machinery can lead to cell-type specific perturbation of cellular function is addressed here by T cell specific ablation of the general U5 snRNP assembly factor CD2BP2/U5-52K. This protein defines the family of nuclear GYF domain containing proteins that are ubiquitously expressed in eukaryotes with essential functions ascribed to early embryogenesis and organ function. Abrogating CD2BP2/U5-52K in T cells, allows us to delineate the consequences of splicing machinery interferences for T cell development and function.

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Article Synopsis
  • In patients with COPD, impaired left ventricular (LV) filling can be categorized into two patterns: small LV size and heart failure with preserved ejection fraction (HFpEF), both linked to increased all-cause mortality.
  • A study involving 1,752 COPD patients found that 8% had small LV, 16% had HFpEF features, and 45% had normal cardiac function, with those having small LV or HFpEF showing significantly higher mortality rates.
  • Small LV is an independent predictor of mortality, contrasting with HFpEF as patients with small LV exhibit reduced LV filling but normal filling pressure and lower biomarker levels.
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Article Synopsis
  • The article talks about how people at protests in South Africa have gotten hurt in the eyes by rubber bullets shot by police.
  • It shares personal stories from three different events to show what happened and how these injuries changed their lives.
  • The article says that using rubber bullets leads to many eye injuries and that the injured people really need more help from doctors, counselors, and legal services.
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Introduction: As with other chronic diseases, the course of chronic obstructive pulmonary disease (COPD) can be expected to be positively influenced if patients are well informed about their disease and undertake appropriate self-management. Assessments of the level of knowledge and management that are comparable should benefit from structured, systematically developed questionnaires. These, however, have not been published in Germany.

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Perfluorodecalin (PFD)-filled capsules have been studied for over 15 years as artificial oxygen carriers. However, none of these capsules combines good biocompatibility, good mechanical stability and dispersion stability. Here we propose to use synthetic triblock peptides containing a central block of cysteine units as a cross-linking shell material for capsules with both good biocompatibility and stability.

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Background: Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma.

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Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility.

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Background: Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.

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Purpose: Failure of transcatheter heart valves (THV) may potentially be treated with repeat transcatheter aortic valve implantation (redo TAVI). We assessed hydrodynamic performance, stability and pinwheeling utilizing the ALLEGRA (New Valve Technology, Hechingen, Germany) THV, a CE approved and marketed THV in Europe, inside different THVs.

Methods: Redo TAVI was simulated with the 27 mm ALLEGRA THV at three implantation depths (-4 mm, 0 mm and +4 mm) in seven different 'failed' THVs: 26 mm Evolut Pro, 25 mm Lotus, 25 mm JenaValve, 25 mm Portico, 23 mm Sapien 3, 27 mm ALLEGRA and M ACURATE neo.

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Background: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD).

Objective: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes.

Methods: We measured eosinophil and neutrophil counts in induced sputum at baseline and 1 year later to stratify 197 adult patients with asthma into 4 inflammatory phenotypes.

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Rationale: In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.

Objectives: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.

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Rationale: Small airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma.

Objective: To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing.

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Background: Extracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited.

Objective: To characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction.

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Background: Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA).

Objective: To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA.

Methods: We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n = 140; severe, n = 128) and 69 healthy controls from the All Age Asthma Cohort.

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Rationale: Asthma, obesity and physical activity (PA) are interrelated. However, longitudinal data with objective PA measures and direct assessment of body composition are still lacking.

Objective: To study the impact of symptom control on PA and body composition.

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Purpose: We recently introduced a sputum cell quality score to rate how cell morphology, cellular debris and squamous cell contamination influence inflammatory cell identification during microscopic evaluation. However, sputum cell quality is generally not considered for the interpretation of sputum fluid phase biomarkers. Therefore, we compared the soluble protein concentrations between sputum samples with different cell quality.

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Background: Anti-T2 biological therapies have proven to effectively reduce acute exacerbations and daily doses of oral steroids in severe eosinophilic asthma. Despite the remarkable clinical efficacy, there are usually only moderate improvements in airflow limitation, suggesting that other measures of lung function like small airway dysfunction (SAD) might better reflect the clinical response. We aimed to investigate if measures of small airway function would predict and correlate with the clinical response to anti-T2 therapy.

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Background: To date, most studies involving high-throughput analyses of sputum in asthma and COPD have focused on identifying transcriptomic signatures of disease. No whole-genome methylation analysis of sputum cells has been performed yet. In this context, the highly variable cellular composition of sputum has potential to confound the molecular analyses.

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