Anne-Marie Kirsten

• MD
• Managing Director at Pulmonary Research Insitute at LungClinic Grosshansdorf

Background The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of...

Zusammenfassung Einleitung Wie bei anderen chronischen Erkrankungen ist auch bei der chronisch-obstruktiven Lungenerkrankung (COPD) zu erwarten, dass der Verlauf positiv beeinflusst wird, wenn die Patienten gut über ihre Erkrankung informiert sind und angemessen damit umgehen. Hierbei dürfte eine vergleichbare Einschätzung des Wissensstands und Umg...

Background MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed m...

This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructi...

Purpose: To investigate morphofunctional chest MRI for the detection and management of incidental pulmonary nodules in participants with chronic obstructive pulmonary disease (COPD). Materials and methods: In this prospective study, 567 participants (mean age, 66 years ± 9 [SD]; 340 men) underwent same-day contrast-enhanced MRI and nonenhanced l...

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

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 ar...

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 ar...

Mustafa Abdo,1 Frauke Pedersen,1,2 Frederik Trinkmann,3,4 Felix JF Herth,3 Klaus F Rabe,1 Anne-Marie Kirsten,2 Henrik Watz2 1LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 2Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN),...

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 ar...

In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome...

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 bas...

We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC)...

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 tes...

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 associat...

Background Little is known about the role of small airway dysfunction (SAD) and its complex relationship with asthma control and physical activity (PA). Objective to investigate the interrelationship between SAD, risk factors of asthma severity, symptom control and PA. Methods We assessed SAD by impulse oscillometry and other sophisticated lung f...

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. Methods In a longitudinal cohort study of the German Center for Lung Research, we ass...

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...

Rational Asthma, obesity and physical activity (PA) are interrelated. However, longitudinal data with objective PA measures and direct assessment of body composition are still lacking.Objectiveto study the impact of asthma severity and symptom control on PA and body composition.Methods In a longitudinal cohort study, we assessed the body compositio...

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...

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 an...

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1–4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiec...

Asthma is a heterogeneous disease encompassing several distinct sub‐phenotypes with different aetiologies and treatment responses, but we are lacking markers to differentiate patient subgroups. MicroRNAs (miRNA) can regulate gene expression post‐transcriptionally. Due to their high stability in body fluids, their easy detection, and their functiona...

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and S...

Background: A hallmark of idiopathic pulmonary fibrosis is the excess accumulation of extracellular matrix in the lungs. Degradation of extracellular matrix generates free-circulating protein fragments called neoepitopes. The aim of the INMARK trial was to investigate changes in neoepitopes as predictors of disease progression in patients with idi...

Background: There are only limited treatment options for patients with non-cystic fibrosis bronchiectasis (non-CF BE). Human neutrophil elastase (HNE) is a mediator of tissue destruction in non-CF BE. BAY 85-8501, a selective and reversible HNE inhibitor, could represent a new treatment option for this disease. Methods: This was a phase 2a, rand...

The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD). This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmo...

The goal of pharmacologic therapy of stable chronic obstructive pulmonary disease (COPD) is to reduce symptoms, improve exercise intolerance and health-related quality of life, and to reduce exacerbations. Inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are equally effective for the symptomatic management of C...

Background and purpose Fixed-dose combinations of a long-acting beta agonist and an inhaled corticosteroid are more effective than the individual components in COPD. The primary study objective was to demonstrate that the combination indacaterol acetate/mometasone furoate (IND/MF [QMF149]) was non-inferior to the twice-daily combination salmeterol...

Timm Greulich,1 Sina Mager,1 Tanja Lucke,2 Andreas Rembert Koczulla,1 Robert Bals,3 Sebastian Fähndrich,3 Rudolf A Jörres,2 Peter Alter,1 Anne Kirsten,4 Claus Franz Vogelmeier,1 Henrik Watz4 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps-University, Member of the German Centre...

Background: A subset of COPD-patients presents with eosinophilic airway inflammation. While treatment of asthmatic patients with the GATA3-specific DNAzyme SB010 attenuated sputum eosinophilia after allergen challenge, this specific treatment has not been evaluated in patients with COPD. Our objective was to evaluate the feasibility and safety of...

Background: The TORRACTO®study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. Methods: The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg)...

Background: Little is known about physical activity in daily life among patients with sarcoidosis. Fatigue is a frequent and disabling symptom that might negatively affect physical activity levels. Methods: In patients with sarcoidosis, we measured physical activity (steps per day) by accelerometry (SenseWear Armband) for 1 week. We assessed lun...

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was −125.4 mL...

Background Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy. Methods The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20–44 years (29 centres in 13 Euro...

Background: Dyspnea is the impairing cardinal symptom in COPD, but the underlying brain mechanisms and their relationships to clinical patient characteristics are widely unknown. This study compared neural responses to the perception and anticipation of dyspnea between patients with stable moderate-to-severe COPD and healthy controls. Moreover, ass...

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expirato...

Background: While current therapies reduce symptoms in chronic obstructive pulmonary disease (COPD) patients, substantial unmet need remains and novel treatments are highly desired. Phosphoinositide 3-kinase δ (PI3Kδ) is a lipid kinase specifically expressed in leucocytes and involved in their recruitment and activation. This study evaluated the s...

Background Physical activity (PA) is associated with disease severity in idiopathic pulmonary fibrosis (IPF), but longitudinal studies evaluating its prognostic value and changes over time are lacking. Methods We measured PA (steps per day, SPD) in a cohort of 46 IPF-patients (mean age, 67 years; mean FVC, 76.1%pred.) by accelerometry at baseline,...

Background A previous Phase IIIb study (NCT1462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo. This post hoc analysis was performed to assess the effect of treatment in...

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease. For each patient, four of five treatments were administered once daily for 6 weeks, with a 2...

Background Sleep disturbances are common in patients with chronic obstructive pulmonary disease (COPD) with a considerable negative impact on their quality of life. However, factors associated with measures of sleep in daily life have not been investigated before nor has the association between sleep and the ability to engage in physical activity o...

Asthma is a chronic airway disease with a heterogeneous clinical presentation [1], and a subset of ∼5–10% of patients suffer from severe disease [2]. Chronic obstructive pulmonary disease (COPD) is different from asthma with respect to underlying pathobiology but shares some clinical features with severe asthma, for instance fixed airway obstructio...

Background: Long-acting bronchodilators, including anticholinergics glycopyrronium and tiotropium, are central to symptomatic management of chronic obstructive pulmonary disease (COPD). In patients with moderate to severe COPD, glycopyrronium has demonstrated comparable efficacy to open-label and single-blinded tiotropium, but with faster onset of...

Introduction The coexistence of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) is frequent and might be inter-related through inflammation-related processes reflected by specific markers. Here, we studied angiopoietin-like protein 4 (ANGPTL4), an upcoming cardiovascular marker, in stable COPD, and its relationship to...

BACKGROUND: Physical activity (PA) has been extensively investigated in COPD, curiously there is very limited data for asthma. AIMS: We aimed to investigate levels of PA in adult asthmatics, and to identify associations between PA and lung function. METHODS: We measured PA (steps per day, SPD) in 146 stable asthma patients (severe asthma/SA, n=63;...

BACKGROUND: The observed coexistence of COPD and cardiovascular disease (CVD) may be interrelated through inflammatory processes. Here we investigated the relationship between angiopoietin-like protein 4 (ANGPTL4), an acute phase protein, and cardiovascular function in patients with COPD. METHODS: In a cohort study we assessed serum levels of ANGP...

Background: Aclidinium bromide 400 µg (AB) is known to improve lung function and symptoms in moderate to severe COPD; however, sleep disturbances are common in patients with COPD. Aim: This study investigated the effects of AB on symptoms and sleep quality. Methods: This was a Phase IV, 21-day, randomized, double-blind, placebo (PBO)-controlled, tw...

Background: Modulating excessive airway neutrophilia might have beneficial effects in neutrophilic airway diseases. In humans the effects of CXCR2 antagonism are well characterized in peripheral blood and sputum, but there are no data on human bronchial mucosa. Methods: We conducted an exploratory, single centre, open-label, non-controlled, pilot s...

Background: Inhibition of excessive neutrophil elastase (NE) might represent a therapeutic approach in neutrophilic airway diseases such as non-cystic fibrosis bronchiectasis (NCFB). Methods: We conducted a multicenter, phase IIa, randomized, double-blind, placebo-controlled, parallel-group study in patients with NCFB. Primary endpoint was safety a...

The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was compared with that of salmeterol/fluticasone propionate in patients with stable, moderate-to-severe chronic obstructive pulmonary disease (COPD). AFFIRM COPD (Aclidinium and Formoterol Findings in Respiratory Medicine COPD) was a 24-week, double-blind, double-dummy, a...

Background: Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the once-daily long-acting β2-agonist olodaterol 5 μg and 10 μg on constant work-rate cycle endurance in patients with moderate to very severe chronic obstructive pulmonary disease. Methods: Patients received placebo, olodaterol 5 μg once...

Background Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality. Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance. However, none of these studies were designed with ph...

Background: Little is known about the consequences of idiopathic pulmonary fibrosis (IPF) for physical activity (PA). Objectives: We aimed to investigate levels of PA in IPF and to study associations of PA with lung function, exercise capacity, symptoms, and quality of life. Methods: In stable patients with IPF we measured PA (steps per day, S...

Background: Blood eosinophil counts might predict response to inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. We used data from the WISDOM trial to assess whether patients with COPD with higher blood eosinophil counts would be more likely to have exacerbations if ICS treat...

Rationale Sporadic lymphangioleiomyomatosis (LAM) is an orphan lung disease for which daily physical activity has not been studied so far and it is unclear whether a disease-specific impact beyond airflow limitation exists. Clinical correlates indicating reduced physical activity in addition to established parameters like airflow limitation and hyp...

Background: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper s...