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1.  “Take the active option” to support Healthy Lungs for Life 
Breathe  2015;11(3):179-181.
In 2014, we were proud to launch the European Respiratory Society (ERS)/European Lung Foundation (ELF) campaign: Healthy Lungs for Life (HLfL;; a lung health campaign to educate all stakeholders about the importance of prevention and management of lung disease and how this can be achieved. Our inaugural theme, “Breathe Clean Air”, was a timely and impactful topic to kick off with and resonated across the globe with politicians in the EU, journalists in a range of countries, scientists carrying out research with funding from HLfL, the people of Munich who had their lungs tested while the ERS International Congress took place, and those who attended events held by our collaborators across the globe, from India to the USA to New Zealand.
ERS/ELF say “take the active option” for Healthy Lungs for Life
PMCID: PMC4666448  PMID: 26634000
2.  Impact of cardiovascular comorbidities on COPD Assessment Test (CAT) and its responsiveness to pulmonary rehabilitation in patients with moderate to very severe COPD: protocol of the Chance study 
BMJ Open  2015;5(7):e007536.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Patients with COPD are characterised by a reduced health status, which can be easily assessed by the COPD Assessment Test (CAT). Previous studies show that health status can be worsened by the presence of comorbidities. However, the impact of cardiovascular comorbidities on health status as assessed with CAT is not sufficiently investigated. Therefore, the current study has the following objectives: (1) to study the clinical, (patho)physiological and psychosocial determinants of the CAT, and impact of previously established and/or newly diagnosed cardiovascular comorbidities on health status in tertiary care patients with COPD; (2) to assess the effects of pulmonary rehabilitation on CAT scores in patients with COPD; (3) to develop reference values for the CAT in Dutch elderly patients without COPD; and (4) to validate the CAT in a broad sample of Dutch patients with COPD.
Methods and analysis
The COPD, Health status and Comorbidities (Chance) study is a monocentre study consisting of an observational cross-sectional part and a longitudinal part. Demographic and clinical characteristics will be assessed in primary care, secondary care and tertiary care patients with COPD, and in patients without COPD. To assess health status, the CAT, Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) will be used. The longitudinal part consists of a comprehensive pulmonary rehabilitation programme in 500 tertiary care patients. For the cross-sectional part of the study, 150 patients without COPD, 100 primary care patients and 100 secondary care patients will be assessed during a single home visit.
Ethics and dissemination
The Medical Ethical Committee of the Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands (METC 11-3-070), has approved this study. The study has been registered at the Dutch Trial Register (NTR 3416).
PMCID: PMC4513521  PMID: 26198426
Chronic Obstructive Pulmonary Disease; COPD assessment test; Health status; Cardiovascular comorbidities
3.  How to carry out a field walking test in chronic respiratory disease 
Breathe  2015;11(2):128-139.
Educational Aims
To provide recommendations for conducting field walking tests in people with chronic respiratory disease, from the new European Respiratory Society/American Thoracic Society Technical Standard
To provide information to assist in selecting a field walking test in people with chronic respiratory disease.
Key points
The 6MWT, ISWT and ESWT are valid and reliable tests of functional exercise capacity in people with COPD. The 6MWT is also widely used in other chronic respiratory disorders.
There is a learning effect for the 6MWT and ISWT, so two tests must be performed if the tests are being used to measure change over time, with the best distance recorded.
The 6MWT is very sensitive to changes in the way it is conducted, including use of encouragement, provision of supplemental oxygen, changes in track layout and length, and use of wheeled walkers. These factors should be held constant when the test is repeated.
The 6MWT, ISWT and ESWT are strenuous tests, with cardiorespiratory responses that are similar to those during a maximal incremental exercise test. As a result, the contraindications and precautions for these field walking tests should be the same as for a laboratory-based incremental exercise test.
The European Respiratory Society (ERS) and American Thoracic Society (ATS) have recently published a Technical Standard which documents the standard operating procedures for the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT). The Technical Standard shows that all three tests are valid and reliable measures of functional exercise capacity in people with chronic respiratory disease and makes recommendations for standardising their performance. Key findings and recommendations of the Technical Standard include: The 6MWT, ISWT and ESWT are strenuous tests which elicit cardiorespiratory responses that are similar to those observed during a maximal incremental exercise test. As a result, the contraindications and precautions for field walking tests should be consistent with those used for a laboratory-based incremental exercise test.There is strong evidence of a learning effect for the 6MWT and ISWT. Two tests should be performed when the 6MWT or ISWT are used to measure change over time.The 6MWT, ISWT and ESWT are responsive to treatment effects in people with chronic respiratory disease, particularly for rehabilitation.The 6MWT is very sensitive to variations in methodology, including use of encouragement, provision of supplemental oxygen, changes in track layout and length, and use of wheeled walkers. These factors should be documented and held constant on repeat testing.The lowest SpO2 recorded during a 6MWT is an important marker of disease severity and prognosis. Continuous pulse oximetry is recommended during the 6MWT, to ensure that the lowest SpO2 is recorded.In adults with chronic respiratory disease, a change in 6-min walk distance of 30 m or more indicates a clinically significant change has occurred.
PMCID: PMC4487379  PMID: 26306113
4.  An observational, longitudinal study on the home environment of people with chronic obstructive pulmonary disease: the research protocol of the Home Sweet Home study 
BMJ Open  2014;4(11):e006098.
Chronic obstructive pulmonary disease (COPD) represents an important public health challenge. Patients are confronted with limitations during activities of daily living (ADLs). Resident loved ones of patients with COPD may be uniquely positioned to witness these limitations. COPD may have an impact on not only the patients’ life, but also on the lives of the resident loved ones. Furthermore, COPD exacerbation-related hospital admissions often occur in patients with COPD. However, whether and to what extent these admissions influence resident loved ones’ burden and health status remains currently unknown. Therefore, the primary objectives of this study are to investigate the differences between patients with COPD and resident loved ones’ perceptions of patients’ health status and problematic ADLs and to study prospectively the effects of a COPD exacerbation on resident loved ones’ perceptions of patients’ health status and problematic ADLs.
Methods and analysis
An observational, longitudinal study will be performed in 192 patients with COPD and their 192 resident loved ones. Primary outcomes are daily functioning, ADL, disease-specific health status, generic health status and dyspnoea. These will be assessed during home visits at baseline and after 12 months. Additional home visits will be performed when a COPD exacerbation-related hospital admission occurs during the 12-month follow-up period.
Ethics and dissemination
This protocol was approved by the Medical Ethics Committee of the Catharina Hospital Eindhoven, the Netherlands (NL42721.060.12/M12-1280) and is registered in the Dutch Trial Register (NTR3941).
PMCID: PMC4244479  PMID: 25384686
Chronic Obstructive Pulmonary Disease; Home environment; Resident loved one; Family caregiver; Activities of Daily Living; Quality of Life
5.  An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease 
Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications.
Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD.
Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards.
Results: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality.
Conclusions: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.
PMCID: PMC4098112  PMID: 24787074
6.  Metabolic load during strength training or NMES in individuals with COPD: results from the DICES trial 
BMC Pulmonary Medicine  2014;14:146.
Strength training and neuromuscular electrical stimulation (NMES) are effective training modalities for improving muscle function, exercise performance and health status in individuals with COPD. The aim of the present study was to analyze the metabolic load of these training modalities at baseline, half-way, and at the end of an eight-week interdisciplinary pulmonary rehabilitation program in a subgroup of individuals with COPD of the DICES trial.
Of 24 individuals with COPD (FEV1: 34 ± 2% predicted, men: 58%, age: 66 (61–68) years), peak oxygen uptake (VO2), peak minute ventilation (VE), heart rate, oxygen saturation and symptom scores were assessed during HF-NMES (75 Hz), LF-NMES (15 Hz) and strength training at three moments during their pulmonary rehabilitation program.
Intervention-related peak VO2 did not change over time during HF-NMES, LF-NMES or strength training. Intervention-related peak VE did not change over time during strength training or LF-NMES and increased slightly, but significantly over time during HF-NMES. Peak VO2 and VE were significantly higher during strength training compared to HF-NMES or LF-NMES. Oxygen saturation significantly decreased after the first measurements during HF-NMES and strength training group to baseline, while no significant changes in oxygen saturation were observed during the other measurements. Heart rate significantly increased compared to baseline in all groups at all moments and was significantly higher after strength training compared to HF-NMES or LF-NMES. Median end scores (points) for dyspnea, fatigue and muscle pain ranged from 1 to 3, from 0.5 to 2 and from 0 to 6 after HF-NMES, from 2 to 3, from 2 to 5 and from 0 to 9 after LF-NMES and from 2 to 5, from 1.5 to 4 and from 0 to 28 after strength training respectively.
To conclude, the metabolic load and symptom scores remain acceptable low over time with increasing training loads during HF-NMES, LF-NMES or strength training.
Trial registration
Trial registration:NTR2322
PMCID: PMC4236758  PMID: 25182377
Chronic obstructive pulmonary disease; Neuromuscular electrical stimulation; Pulmonary rehabilitation; Strength training
7.  Prevalence of Metabolic Syndrome in COPD Patients and Its Consequences 
PLoS ONE  2014;9(6):e98013.
The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied. We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects.
228 COPD patients and 156 healthy subjects were included. Metabolic syndrome was defined using criteria of the IDF. In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed. Groups were stratified for BMI and gender.
Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects. After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers. Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome. Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups. In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without.
Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects. Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities.
PMCID: PMC4064974  PMID: 24950070
8.  Characteristics and determinants of endurance cycle ergometry and six-minute walk distance in patients with COPD 
Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD). We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients.
A dataset of 2053 COPD patients (43% female, age: 66.9 ± 9.5 years, FEV1% predicted: 48.2 ± 23.2) was analyzed retrospectively. Patients underwent, amongst others, respiratory function evaluation; medical tests and questionnaires, one maximal incremental cycle test where peak work rate was determined and two functional exercise tests: a CET at 75% of peak work rate and 6MWT. A stepwise multiple linear regression was used to assess determinants.
On average, patients had impaired exercise tolerance (peak work rate: 56 ± 27% predicted, 6MWT: 69 ± 17% predicted). A total of 2002 patients had CET time of duration (CET-Tend) less than 20 min while only 51 (2.5%) of the patients achieved 20 min of CET-Tend . In former patients, the percent of predicted peak work rate achieved differed significantly between men (48 ± 21% predicted) and women (67 ± 31% predicted). In contrast, CET-Tend was longer in men (286 ± 174 s vs 250 ± 153 s, p < 0.001). Also, six minute walking distance (6MWD) was higher in men compared to women, both in absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m, 72%predicted, p < 0.05). Gender was associated with the CET-Tend but BMI, FEV1 and FRC were related to the 6MWD highlighting the different determinants of exercise performance between CET and 6MWT.
CET-Tend is a valuable outcome of CET as it is related to multiple clinical aspects of disease severity in COPD. Gender difference should temper the interpretation of CET.
PMCID: PMC4229855  PMID: 24885117
Exercise; 6MWT; CET; CPET; COPD
9.  The COgnitive-Pulmonary Disease (COgnitive-PD) study: protocol of a longitudinal observational comparative study on neuropsychological functioning of patients with COPD 
BMJ Open  2014;4(3):e004495.
Intact cognitive functioning is necessary for patients with chronic obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle guidelines, to make informed decisions and subsequently act on it. Nevertheless, brain abnormalities and cognitive impairment have been found in patients with COPD. To date, it remains unknown which cognitive domains are affected and what the possible consequences are of cognitive impairment. Therefore, objectives of the study described are to determine neuropsychological functioning in patients with COPD, and its influence on health status, daily functioning and pulmonary rehabilitation outcome. Furthermore, structural and functional brain abnormalities and the relationship with cognitive and daily functioning will be explored.
Methods and analysis
A longitudinal observational comparative study will be performed in 183 patients with COPD referred for pulmonary rehabilitation and in 90 healthy control participants. Demographic and clinical characteristics, activities of daily living and knowledge about COPD will be assessed. Baseline cognitive functioning will be compared between patients and controls using a detailed neuropsychological testing battery. An MRI substudy will be performed to compare brain abnormalities between 35 patients with COPD with cognitive impairment and 35 patients with COPD without cognitive impairment. Patients will be recruited between November 2013 and November 2015.
Ethics and dissemination
The study has been approved by the Medical Ethics Committee of the University Hospital Maastricht and Maastricht University (NL45127.068.13/METC 13-3-035) and is registered in the Dutch trial register. All participants will provide written informed consent and can withdraw from the study at any point in time. Assessment and home visit data material will be managed anonymously. The results obtained can be used to optimise patient-oriented treatment for cognitively impaired patients with COPD. The findings will be disseminated in international peer-reviewed journals and through research conferences.
PMCID: PMC3948451  PMID: 24589828
Respiratory Medicine (see Thoracic Medicine); Neuropathology
10.  A randomised controlled trial on the efficacy of advance care planning on the quality of end-of-life care and communication in patients with COPD: the research protocol 
BMJ Open  2014;4(1):e004465.
Recent research shows that advance care planning (ACP) for patients with chronic obstructive pulmonary disease (COPD) is uncommon and poorly carried out. The aim of the present study was to explore whether and to what extent structured ACP by a trained nurse, in collaboration with the chest physician, can improve outcomes in Dutch patients with COPD and their family.
Methods and analysis
A multicentre cluster randomised controlled trial in patients with COPD who are recently discharged after an exacerbation has been designed. Patients will be recruited from three Dutch hospitals and will be assigned to an intervention or control group, depending on the randomisation of their chest physician. Patients will be assessed at baseline and after 6 and 12 months. The intervention group will receive a structured ACP session by a trained nurse. The primary outcomes are quality of communication about end-of-life care, symptoms of anxiety and depression, quality of end-of-life care and quality of dying. Secondary outcomes include concordance between patient's preferences for end-of-life care and received end-of-life care, and psychological distress in bereaved family members of deceased patients. Intervention and control groups will be compared using univariate analyses and clustered regression analysis.
Ethics and dissemination
Ethical approval was received from the Medical Ethical Committee of the Catharina Hospital Eindhoven, the Netherlands (NL42437.060.12). The current project provides recommendations for guidelines on palliative care in COPD and supports implementation of ACP in the regular clinical care.
Clinical trial registration number
PMCID: PMC3902375  PMID: 24384905
Advance Care Planning; End-of-life Care; Palliative Care; COPD
11.  Metabolic and Structural Changes in Lower-Limb Skeletal Muscle Following Neuromuscular Electrical Stimulation: A Systematic Review 
PLoS ONE  2013;8(9):e69391.
Transcutaneous neuromuscular electrical stimulation (NMES) can be applied as a complementary intervention to regular exercise training programs. A distinction can be made between high-frequency (HF) NMES and low-frequency (LF) NMES. In order to increase understanding of the mechanisms of functional improvements following NMES, the purpose of this study was to systematically review changes in enzyme activity, muscle fiber type composition and muscle fiber size in human lower-limb skeletal muscles following only NMES.
Trials were collected up to march 2012 and were identified by searching the Medline/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL and The Physical Therapy Evidence Database (PEDro) databases and reference lists. 18 trials were reviewed in detail: 8 trials studied changes in enzyme activities, 7 trials studied changes in muscle fiber type composition and 14 trials studied changes in muscle fiber size following NMES.
The methodological quality generally was poor, and the heterogeneity in study design, study population, NMES features and outcome parameters prohibited the use of meta-analysis. Most of the LF-NMES studies reported significant increases in oxidative enzyme activity, while the results concerning changes in muscle fiber composition and muscle size were conflicting. HF-NMES significantly increased muscle size in 50% of the studies.
NMES seems to be a training modality resulting in changes in oxidative enzyme activity, skeletal muscle fiber type and skeletal muscle fiber size. However, considering the small sample sizes, the variance in study populations, the non-randomized controlled study designs, the variance in primary outcomes, and the large heterogeneity in NMES protocols, it is difficult to draw definitive conclusions about the effects of stimulation frequencies on muscular changes.
PMCID: PMC3760845  PMID: 24019860
13.  Correlations between disease-specific and generic health status questionnaires in patients with advanced COPD: a one-year observational study 
Longitudinal studies analyzing the correlations between disease-specific and generic health status questionnaires at different time points in patients with advanced COPD are lacking. The aim of this study was to determine whether and to what extent a disease-specific health status questionnaire (Saint George’s Respiratory Questionnaire, SGRQ) correlates with generic health status questionnaires (EuroQol-5-Dimensions, EQ-5D; Assessment of Quality of Life instrument, AQoL; Medical Outcomes Study 36-Item Short-Form Health Survey, SF-36) at four different time points in patients with advanced COPD; and to determine the correlation between the changes in these questionnaires during one-year follow-up.
Demographic and clinical characteristics were assessed in 105 outpatients with advanced COPD at baseline. Disease-specific health status (SGRQ) and generic health status (EQ-5D, AQoL, SF-36) were assessed at baseline, four, eight, and 12 months. Correlations were determined between SGRQ and EQ-5D, AQoL, and SF-36 scores and changes in these scores. Agreement in direction of change was assessed.
Eighty-four patients (80%) completed one-year follow-up and were included for analysis. SGRQ total score and EQ-5D index score, AQoL total score and SF-36 Physical Component Summary measure (SF-36 PCS) score were moderately to strongly correlated. The correlation of the changes between the SGRQ total score and EQ-5D index score, AQoL total score, SF-36 PCS, and SF-36 Mental Component Summary measure (SF-36 MCS) score were weak or absent. The direction of changes in SGRQ total scores agreed slightly with the direction of changes in EQ-5D index score, AQoL total score, and SF-36 PCS score.
At four, eight and 12 months after baseline, SGRQ total scores and EQ-5D index scores, AQoL total scores and SF-36 PCS scores were moderately to strongly correlated, while SGRQ total scores were weakly correlated with SF-36 MCS scores. The correlations between changes over time were weak or even absent. Disease-specific health status questionnaires and generic health status questionnaires should be used together to gain complete insight in health status and changes in health status over time in patients with advanced COPD.
PMCID: PMC3493349  PMID: 22909154
Chronic obstructive pulmonary disease; Health-related quality of life; St. George’s Respiratory Questionnaire; Health status; Disease-specific health status; Generic health status
14.  Effects of Body Mass Index on Task-Related Oxygen Uptake and Dyspnea during Activities of Daily Life in COPD 
PLoS ONE  2012;7(7):e41078.
Patients with COPD use a higher proportion of their peak aerobic capacity during the performance of domestic activities of daily life (ADLs) compared to healthy peers, accompanied by a higher degree of task-related symptoms. To date, the influence of body mass index (BMI) on the task-related metabolic demands remains unknown in patients with COPD. Therefore, the aim of our study was to determine the effects of BMI on metabolic load during the performance of 5 consecutive domestic ADLs in patients with COPD.
Ninety-four COPD patients and 20 healhty peers performed 5 consecutive, self-paced domestic ADLs putting on socks, shoes and vest; folding 8 towels; putting away groceries; washing up 4 dishes, cups and saucers; and sweeping the floor for 4 min. Task-related oxygen uptake and ventilation were assessed using a mobile oxycon, while Borg scores were used to assess task-related dyspnea and fatigue.
Principal Findings
1. Relative task-related oxygen uptake after the performance of domestic ADLs was increased in patients with COPD compared to healthy elderly, whereas absolute oxygen uptake is similar between groups; 2. Relative oxygen uptake and oxygen uptake per kilogram fat-free mass were comparable between BMI groups; and 3. Borg symptom scores for dyspnea en fatigue were comparable between BMI groups.
Patients with COPD in different BMI groups perform self-paced domestic ADLs at the same relative metabolic load, accompanied by comparable Borg symptom scores for dyspnea and fatigue.
PMCID: PMC3398871  PMID: 22815922
15.  Differences in Walking Pattern during 6-Min Walk Test between Patients with COPD and Healthy Subjects 
PLoS ONE  2012;7(5):e37329.
To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects.
Methodology/Principal Findings
79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%).
COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD.
PMCID: PMC3356256  PMID: 22624017
18.  Determinants of polypharmacy and compliance with GOLD guidelines in patients with chronic obstructive pulmonary disease 
Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD.
Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009. Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status.
In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included. On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores. FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy. Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages. Use of corticosteroids was not restricted to patients with frequent exacerbations.
Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms. In addition to severity of disease, health status is an independent predictor of polypharmacy. Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines.
PMCID: PMC3206765  PMID: 22069360
chronic obstructive pulmonary disease; management; pharmacotherapy; polypharmacy; pulmonary rehabilitation; respiratory drug use
19.  Impaired health status and care dependency in patients with advanced COPD or chronic heart failure 
Quality of Life Research  2011;20(10):1679-1688.
Aims of this cross-sectional study were to assess health status and care dependency in patients with advanced chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF) and to identify correlates of an impaired health status.
The following outcomes were assessed in outpatients with advanced COPD (n = 105) or CHF (n = 80): clinical characteristics; general health status (EuroQol-5 Dimensions (EQ-5D); Assessment of Quality of Life instrument (AQoL); Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)); disease-specific health status (St. Georges Respiratory Questionnaire (SGRQ), Minnesota Living with Heart Failure Questionnaire (MLHFQ)); physical mobility (timed ‘Up and Go’ test); and care dependency (Care Dependency Scale).
Patients with advanced COPD or CHF have an impaired health status and may be confronted with care dependency. Multiple regression analyses have shown that physical and psychological symptoms, care dependency and number of drugs were correlated with impaired health status in advanced COPD or CHF, while demographic and clinical characteristics like age, gender, disease severity and co-morbidities were not correlated.
Clinical care should regularly assess symptom burden and care dependency to identify patients with advanced COPD or CHF at risk for an impaired health status.
PMCID: PMC3220822  PMID: 21442430
Chronic obstructive pulmonary disease; Chronic heart failure; Health status; Health-related quality of life; Care dependency; Functional status
20.  Task-related oxygen uptake and symptoms during activities of daily life in CHF patients and healthy subjects 
European Journal of Applied Physiology  2011;111(8):1679-1686.
Patients with chronic heart failure (CHF) have a significantly lower peak aerobic capacity compared to healthy subjects, and, may therefore experience more inconvenience during the performance of domestic activities of daily life (ADLs). To date, the extent to which task-related oxygen uptake, heart rate, ventilation and symptoms during the performance of ADLs in CHF patients is different than in healthy subjects remains uncertain. General demographics, pulmonary function, body composition and peak aerobic capacity were assessed in 23 CHF outpatients and 20 healthy peers. In addition, the metabolic requirement of five simple self-paced domestic ADLs was assessed using a mobile oxycon. Task-related oxygen uptake (ml/min) was similar or lower in CHF patients compared to healthy subjects. In contrast, patients with CHF performing ADLs consumed oxygen at a higher proportion of their peak aerobic capacity than healthy subjects (p < 0.05). For example, getting dressed resulted in a mean task-related oxygen uptake of 49% of peak aerobic capacity, while sweeping the floor resulted in a mean task-related oxygen uptake of 52% of peak aerobic capacity, accompanied by significantly higher Borg symptom scores for dyspnea and fatigue (p < 0.05). Patients with CHF experience use a higher proportion of their peak aerobic capacity, peak ventilation and peak heart rate during the performance of simple self-paced domestic ADL than their healthy peers. These findings represent a necessary step in improving our understanding of improving what troubles patients the most—not being able to do the things that they could when they were healthy.
PMCID: PMC3156911  PMID: 21210281
Self-paced; ADL; Domestic; Chronic heart failure
21.  Nordic Walking improves daily physical activities in COPD: a randomised controlled trial 
Respiratory Research  2010;11(1):112.
In patients with COPD progressive dyspnoea leads to a sedentary lifestyle. To date, no studies exist investigating the effects of Nordic Walking in patients with COPD. Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages. Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity.
Sixty COPD patients were randomised to either Nordic Walking or to a control group. Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention. Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD). Assessment time points in both groups: baseline, after three, six and nine months.
After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01). Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01). These significant improvements were sustained six and nine months after baseline. In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.
Nordic Walking is a feasible, simple and effective physical training modality in COPD. In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.
Clinical trial registration
Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632
PMCID: PMC2933683  PMID: 20727209
22.  End-of-life care in a COPD patient awaiting lung transplantation: a case report 
COPD is nowadays the main indication for lung transplantation. In appropriately selected patients with end stage COPD, lung transplantation may improve quality of life and prognosis of survival. However, patients with end stage COPD may die while waiting for lung transplantation. Palliative care is important to address the needs of patients with end stage COPD. This case report shows that in a patient with end stage COPD listed for lung transplantation offering palliative care and curative-restorative care concurrently may be problematic. If the requirements to remain a transplantation candidate need to be met, the possibilities for palliative care may be limited. Discussing the possibilities of palliative care and the patient's treatment preferences is necessary to prevent that end-of-life care needs of COPD patients dying while listed for lung transplantation are not optimally addressed. The patient's end-of-life care preferences may ask for a clear distinction between the period in which palliative and curative-restorative care are offered concurrently and the end-of-life care period. This may be necessary to allow a patient to spend the last stage of life according to his or her wishes, even when this implicates that lung transplantation is not possible anymore and the patient will die because of end stage COPD.
PMCID: PMC2873495  PMID: 20426832
23.  Whole-Body versus Local DXA-Scan for the Diagnosis of Osteoporosis in COPD Patients 
Journal of Osteoporosis  2010;2010:640878.
Background. Osteoporosis is an extrapulmonary effect of chronic obstructive pulmonary disease (COPD). Diagnosis of osteoporosis is based on BMD measured by DXA-scan. The best location for BMD measurement in COPD has not been determined. Aim of this study was to assess whole-body BMD and BMD of the hip and lumbar spine (local DXA) in COPD patients and compare the prevalence of osteoporosis at these locations. Methods. Whole body as well as local DXA-scan were made in 168 COPD patients entering pulmonary rehabilitation. Patient-relevant characteristics were assessed. Prevalence of osteoporosis was determined. Characteristics of patients without osteoporosis were compared to patients with osteoporosis on local DXA. Results. A higher prevalence of osteoporosis was found using local DXA compared to whole-body DXA (39% versus 21%). One quarter of patients without osteoporosis on whole body-DXA did have osteoporosis on local DXA. Significant differences in patient characteristics between patients without osteoporosis based on both DXA measurements and patients with osteoporosis based on local DXA only were found. Conclusions. DXA of the hip and lumbar spine should be made to assess bone mineral density in COPD patients. The lowest T-score of these locations should be used to diagnose osteoporosis.
PMCID: PMC2957150  PMID: 20976078
24.  IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study 
BMC Medical Genetics  2009;10:23.
Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.
The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).
Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers. Plasma levels of CRP, IL-6 and FG were measured in the total study group. Differences in haplotype distributions were tested using the global and haplotype-specific statistics.
Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients. However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile). Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003). Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005). None of the genes were associated with COPD-related phenotypes.
Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation.
PMCID: PMC2660301  PMID: 19272152
25.  Self-perceived symptoms and care needs of patients with severe to very severe chronic obstructive pulmonary disease, congestive heart failure or chronic renal failure and its consequences for their closest relatives: the research protocol 
Recent research shows that the prevalence of patients with very severe chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and chronic renal failure (CRF) continues to rise over the next years. Scientific studies concerning self-perceived symptoms and care needs in patients with severe to very severe COPD, CHF and CRF are scarce.
Consequently, it will be difficult to develop an optimal patient-centred palliative care program for patients with end-stage COPD, CHF or CRF. The present study has been designed to assess the symptoms, care needs, end-of-life care treatment preferences and communication needs of patients with severe to very severe COPD, CHF or CRF. Additionally, family distress and care giving burden of relatives of these patients will be assessed.
A cross-sectional comparative and prospective longitudinal study in patients with end-stage COPD, CHF or CRF has been designed. Patients will be recruited by their treating physician specialist. Patients and their closest relatives will be visited at baseline and every 4 months after baseline for a period of 12 months. The following outcomes will be assessed during home visits: self-perceived symptoms and care needs; daily physical functioning; general health status; end-of-life care treatment preferences; end-of-life care communication and care-giver burden of family caregivers. Additionally, end-of-life care communication and prognosis of survival will be assessed with the physician primarily responsible for the management of the chronic organ failure. Finally, if patients decease during the study period, the baseline preferences with regard to life-sustaining treatments will be compared with the real end-of-life care.
To date, the symptoms, care needs, caregiver burden, end-of-life care treatment preferences and communication needs of patients with very severe COPD, CHF or CRF remain unknown. The present study will increase the knowledge about the self-perceived symptoms, care-needs, caregiver burden, end-of-life care treatment preferences and communication needs from the views of patients, their loved ones and their treating physician. This knowledge is necessary to optimize palliative care for patients with COPD, CHF or CRF. Here, the design of the present study has been described. A preliminary analysis of the possible strengths, weaknesses and clinical consequences is outlined.
PMCID: PMC2391145  PMID: 18460203

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