Background: Despite the urgent need for palliative care for patients with advanced chronic obstructive pulmonary disease (COPD), it is not yet daily practice. Important factors influencing the... Show moreBackground: Despite the urgent need for palliative care for patients with advanced chronic obstructive pulmonary disease (COPD), it is not yet daily practice. Important factors influencing the provision of palliative care are adequate communication skills, knowing when to start palliative care and continuity of care. In the COMPASSION study, we address these factors by implementing an integrated palliative care approach for patients with COPD and their informal caregivers.Methods: An integrated palliative care intervention was developed based on existing guidelines, a literature review, and input from patient and professional organizations. To facilitate uptake of the intervention, a multifaceted implementation strategy was developed, comprising a toolbox, (communication) training, collaboration support, action planning and monitoring. Using a hybrid effectiveness-implementation type 2 design, this study aims to simultaneously evaluate the implementation process and effects on patient, informal caregiver and professional outcomes. In a cluster randomized controlled trial, eight hospital regions will be randomized to receive the integrated palliative care approach or to provide care as usual. Eligible patients are identified during hospitalization for an exacerbation using the Propal-COPD tool. The primary outcome is quality of life (FACIT-Pal) at 6 months. Secondary outcome measures include spiritual well-being, anxiety and depression, unplanned healthcare use, informal caregiver burden and healthcare professional's self-efficacy to provide palliative care. The implementation process will be investigated by a comprehensive mixed-methods evaluation assessing the following implementation constructs: context, reach, dose delivered, dose received, fidelity, implementation level, recruitment, maintenance and acceptability. Furthermore, determinants to implementation will be investigated using the Consolidated Framework for Implementation Research.Discussion: The COMPASSION study will broaden knowledge on the effectiveness and process of palliative care integration into COPD-care. Furthermore, it will improve our understanding of which strategies may optimize the implementation of integrated palliative care. Show less
Background The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated... Show moreBackground The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care (guideline-supported non-programmatic care). It is possible that only a subset of COPD patients in primary care benefit from IDM. We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time. Method Post-hoc analyses of the RECODE trial among 1086 COPD patients. Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM. We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care. Results Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement. Clinical improvement with IDM was associated with female gender (12-months) and being younger (24-months), and improvement with usual care was associated with having a depression (24-months). Conclusions More severe dyspnea is a key predictor of improved QOL in COPD patients over time. More research is needed to replicate patient characteristics associated with clinical improvement with IDM, such that IDM programs can be offered to patients that benefit the most, and can potentially be adjusted to meet the needs of other patient groups as well. Show less
Disturbances in mitochondrial structure and function in lung epithelial cells have been implicated in the pathogenesis of various lung diseases, including chronic obstructive pulmonary disease ... Show moreDisturbances in mitochondrial structure and function in lung epithelial cells have been implicated in the pathogenesis of various lung diseases, including chronic obstructive pulmonary disease (COPD). Such disturbances affect not only cellular energy metabolism but also alter a range of indispensable cellular homeostatic functions in which mitochondria are known to be involved. These range from cellular differentiation, cell death pathways, and cellular remodeling to physical barrier function and innate immunity. all of which are known to be impacted by exposure to cigarette smoke and have been linked to COPD pathogenesis. Next to their well-established role as the first physical frontline against external insults, lung epithelial cells are immunologically active. Malfunctioning epithelial cells with defective mitochondria are unable to maintain homeostasis and respond adequately to further stress or injury, which may ultimately shape the phenotype of lung diseases. In this review, we provide a comprehensive overview of the impact of cigarette smoke on the development of mitochondrial dysfunction in the lung epithelium and highlight the consequences for cell function, innate immune responses, epithelial remodeling, and epithelial barrier function in COPD. We also discuss the applicability and potential therapeutic value of recently proposed strategies for the restoration of mitochondrial function in the treatment of COPD. Show less
Kuipers, E.; Wensing, M.; Smet, P.A.G.M. de; Teichert, M. 2020
Background: Treatment of obstructive lung disease with inhalation therapy needs changes in patient behavior. Shortly after the start with inhaled corticosteroids (ICS) maintenance therapy, patients... Show moreBackground: Treatment of obstructive lung disease with inhalation therapy needs changes in patient behavior. Shortly after the start with inhaled corticosteroids (ICS) maintenance therapy, patients might be in need of additional pharmaceutical care, tailored to their individual needs. This study aimed to provide insight into patient behavior, goals and perceptions regarding their medical treatment at start with ICS therapy, by telephone interviews with ICS starters. Besides, this study investigated pharmacists' and patients' experiences with these interviews and opinions on the utility of this type of consultation for daily practice.Methods: Semi-structured telephone interviews were conducted by pharmacists with adult patients 2-3 weeks after starting ICS. The Theoretical Domain Framework (TDF) was used for data analysis and coding. Afterward, the patients and pharmacists were questioned about their experiences with the interview.Results: Five pharmacists conducted interviews with 23 ICS starters. Except the domains "environmental context and resources", "optimism", and "reinforcement", the remaining 11 domains in the TDF were addressed in the interviews. The majority of patients defined personal goals, which mainly addressed disease or symptom control (clinical goals). Some patients showed a lack of knowledge regarding the clinical indication or therapy duration. Views on beneficial medication effects differed between patients. Some patients specifically mentioned concerns or anxiety about side effects. The interviewees described different perceptions on the necessity of a personalized routine for regular medication use. Patients and pharmacists both felt positive about an added value of these interviews for daily practice.Conclusion: Patient interviews shortly after start with ICS therapy revealed various perceptions and beliefs that might influence medication use and achievement of individual treatment goals. The patients appreciated the opportunity to ask questions and share their perspectives and needs with their pharmacist, and the pharmacists experienced that the interviews had added value. Show less
OBJECTIVES: Older patients with chronic obstructive pulmonary disease (COPD),hospitalized for an acute exacerbation, often do not receive recommendedpost-acute pulmonary rehabilitation. This... Show moreOBJECTIVES: Older patients with chronic obstructive pulmonary disease (COPD),hospitalized for an acute exacerbation, often do not receive recommendedpost-acute pulmonary rehabilitation. This underuse might be related to theimpaired clinical and functional status of these patients, who are more likely topresent with frailty, comorbidities, and disability. Having developed andimplemented a geriatric rehabilitation program for these patients (GR_COPD), theprimary aim of this study was to investigate the effectiveness of this program.DESIGN AND INTERVENTION: A prospective cohort study with a 3-month follow-upperiod. Patients who declined the GR_COPD program were considered as controls.SETTING AND PARTICIPANTS: The study was conducted at the pulmonary department of2 hospitals. Patients were eligible when hospitalized as a result of an acuteexacerbation of COPD and indicated for the GR_COPD program based on standardizedcriteria.METHODS: Primary outcome was defined as change in disease-specific health statusmeasured with the clinical COPD questionnaire (CCQ), secondary outcome as theexacerbation rate ratio during follow-up. To balance potential confoundersbetween the intervention and control group, propensity score-based weightedlinear regression analyses were performed.RESULTS: Of the 158 included patients [78 (49.4%) male, mean age 70.8 (±8.1)years, mean forced expiratory volume in 1 second: 35.5 (±12.8) as % ofpredicted], 78 received the GR_COPD program. The results of the CCQ showed asignificant and clinically relevant treatment effect of -0.56 points [95%confidence interval (CI) -0.89, -0.23; P = .001). Patients in the control grouphad 2.77 times more exacerbations compared with the intervention group (95% CI2.13, 3.58; P < .001).CONCLUSIONS/IMPLICATIONS: This study shows a clinically relevant effect of theGR_COPD program on disease-specific health status and exacerbation rate.Implementation of the program for older patients with severe COPD hospitalizedfor an acute exacerbation is recommended. Show less
Goossens, L.M.A.; Jonker, M.F.; Rutten-van Molken, M.P.M.H.; Boland, M.R.S.; Slok, A.H.M.; Salome, P.L.; ... ; Res Team Dev ABC Tool 2019
Background In discrete-choice experiments (DCEs), choice alternatives are described by attributes. The importance of each attribute can be quantified by analyzing respondents' choices. Estimates... Show moreBackground In discrete-choice experiments (DCEs), choice alternatives are described by attributes. The importance of each attribute can be quantified by analyzing respondents' choices. Estimates are valid only if alternatives are defined comprehensively, but choice tasks can become too difficult for respondents if too many attributes are included. Several solutions for this dilemma have been proposed, but these have practical or theoretical drawbacks and cannot be applied in all settings. The objective of the current article is to demonstrate an alternative solution, the fold-in, fold-out approach (FiFo). We use a motivating example, the ABC Index for burden of disease in chronic obstructive pulmonary disease (COPD). Methods Under FiFo, all attributes are part of all choice sets, but they are grouped into domains. These are either folded in (all attributes have the same level) or folded out (levels may differ). FiFo was applied to the valuation of the ABC Index, which included 15 attributes. The data were analyzed in Bayesian mixed logit regression, with additional parameters to account for increased complexity in folded-out questionnaires and potential differences in weight due to the folding status of domains. As a comparison, a model without the additional parameters was estimated. Results Folding out domains led to increased choice complexity for respondents. It also gave domains more weight than when it was folded in. The more complex regression model had a better fit to the data than the simpler model. Not accounting for choice complexity in the models resulted in a substantially different ABC Index. Conclusion Using a combination of folded-in and folded-out attributes is a feasible approach for conducting DCEs with many attributes. Show less
Does, A.M. van der; Heijink, M.; Mayboroda, O.A.; Persson, L.J.; Aanerud, M.; Bakke, P.; ... ; Giera, M. 2019
Human blood monocytes are divided into populations based on the differential expression of CD14 and CD16 receptors: CD14 (+) CD16(classical), CD14 (+) CD16 (+) (intermediate), and CD14(-)CD16(+) ... Show moreHuman blood monocytes are divided into populations based on the differential expression of CD14 and CD16 receptors: CD14 (+) CD16(classical), CD14 (+) CD16 (+) (intermediate), and CD14(-)CD16(+) (non-classical). Given their functional differences and their role in pathogenesis of chronic obstructive pulmonary disease (COPD), monocyte profiling is of clinical interest. Here we investigated blood monocyte subsets in clinically stable COPD patients with alpha1-antitrypsin (AAT) deficiency (PiZZ, n = 7) and with normal AAT variant (PiMM, n = 7). Peripheral whole blood was collected in sodium heparin tubes and incubated with LPS (from E. coli; 1 mu g/ml) or placebo for 6 h at 37 degrees C, 5% CO2. To profile monocyte subsets we performed flow cytometry analysis based on HLA-DR and CD14/CD16 staining. HLA-DR + subsets of cells did not differ between PiZZ and PiMM COPD, and healthy controls (n = 7), used as a reference. Monocyte profiling, which express the CD14 and CD16, but not the HLA-DR (HLA-DR-) showed that intermediate monocytes subset was lowest in PiZZ group, and almost totally disappeared from blood treated with LPS. The non-classical subset was almost absent in PiZZ patients independently of LPS treatment. Recent studies demonstrate that non-classical monocytes exhibit a unique ability to protect the vascular endothelium under both homeostatic and inflammatory conditions whereas intermediate monocytes are recruited at a later stage of inflammation, and are associated with secretion of cytokines/chemokines and wound healing. Evident alterations in blood monocyte subsets together with a partial reduction of AAT levels, an important anti-inflammatory protein, can be key factors for the early manifestation of emphysema in some PiZZ AATD carriers. Show less
Does, A.M. van der; Heijink, M.; Mayboroda, O.A.; Persson, L.J.; Aanerud, M.; Bakke, P.; ... ; Giera, M. 2019
Introduction: Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be... Show moreIntroduction: Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis.Objectives: Here we investigated if PUFA metabolism is disturbed in COPD patients.Methods: Free PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed.Results: Significantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling.Conclusions: Our findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD. Show less
AimsLeft ventricular (LV) systolic function is a known prognostic factor after ST-segment elevation myocardial infarction (STEMI). We evaluated the prognostic value of LV global longitudinal strain... Show moreAimsLeft ventricular (LV) systolic function is a known prognostic factor after ST-segment elevation myocardial infarction (STEMI). We evaluated the prognostic value of LV global longitudinal strain (GLS) in patients with chronic obstructive pulmonary disease (COPD) after STEMI.Methods and resultsOne hundred and forty-three STEMI patients with COPD (mean age 70 +/- 11 years, 71% male), were retrospectively analysed. Left ventricular ejection fraction (LVEF) and LV GLS were measured on transthoracic echocardiography within 48 h of admission. Patients were followed for the occurrence of all-cause mortality and the combined endpoint of all-cause mortality and heart failure hospitalization. After a median follow-up of 68 (interquartile range 38.5-99) months, 66 (46%) patients died and 70 (49%) patients reached the combined endpoint. The median LV GLS was-14.4%. Patients with LV GLS >-14.4% (more impaired) showed higher cumulative event rates of all-cause mortality (19%, 26%, and 44% vs. 7%, 8%, and 18% at 1, 2, and 5 years follow-up; log-rank P = 0.004) and the combined endpoint (26%, 34%, and 50% vs. 8%, 10%, and 20% at 1, 2, and 5 years follow-up; log-rank P 0.001) as compared to patients with LV GLS <-14.4%. In multivariate analysis, LV GLS >-14.4% was independently associated with increased all-cause mortality and the combined endpoint [hazard ratio (HR) 2.07; P = 0.02 and HR 2.20; P 0.01, respectively] and had incremental prognostic value over LVEF demonstrated by a significant increase in chi(2) (P = 0.023 and P = 0.011, respectively).ConclusionImpaired LV GLS is independently associated with worse long-term survival in STEMI patients with COPD and has incremental prognostic value over LVEF. Show less
The disease is characterized by a progressive and largely irreversible decline in lung function, which is associated with long-term airway exposures to cytotoxic particles and gasses, such as... Show moreThe disease is characterized by a progressive and largely irreversible decline in lung function, which is associated with long-term airway exposures to cytotoxic particles and gasses, such as cigarette smoke. Microbial colonization and infections are an important pathophysiological aspect in COPD patients. However, the underlying mechanisms linking smoking with microbial colonization and infections in COPD are incompletely understood. The airway epithelium is the first target of inhaled cigarette smoke. Furthermore, epithelial cells are the first defense lining of the respiratory tract that prevents microbial colonization and infections. Therefore, alterations in host defense and airway epithelial remodeling may contribute to COPD development and progression. In this thesis, studies are presented in which the impact of cigarette smoke exposure and COPD disease status on the innate host defense functions of the airway epithelium are explored. This was done by using cell culture experiments in which the effect of cigarette smoke was examined, or in which epithelial cultures of COPD patients and non-COPD (ex)smokers were compared. Show less
Does, A.M. van der; Amatngalim, G.D.; Keijser, B.; Hiemstra, P.S.; Villenave, R. 2018
The studies presented in this thesis were aimed at developing and using in vitro models that could benefit research towards understanding asthma and COPD. We used an in vitro model... Show moreThe studies presented in this thesis were aimed at developing and using in vitro models that could benefit research towards understanding asthma and COPD. We used an in vitro model representing a Th2-high gene signature and studied how this gene signature may be affected by external factors such as cigarette smoke or drugs. Using these in vitro models may help to predict clinical outcomes, although they will require extensive validation. We also investigated the possibility of using primary human airway epithelial cells to model bacterial and viral exacerbations. Whereas this model is currently still under investigation, it could be particularly useful to study possible biomarkers of exacerbations and how these may be affected by external factors. Additionally, we also developed a new method to expand and differentiate mouse tracheal epithelial cells in vitro. Overall, studying airway epithelial cells may provide important clues for understanding disease pathogenesis, lead to identification of new treatment targets, and may provide important biomarkers. Using airway epithelial cells and their derived biomarkers could significantly improve our understanding in disease phenotypes of asthma and COPD. Additionally, with increasing knowledge of the disease phenotypes, we could better address the unmet need in treatment of asthma and COPD. Show less
