Prevalence of dyspnea in general adult populations: A systematic review and meta-analysis.

INTRODUCTION: Dyspnea is a commonly described symptom in various chronic and acute conditions. Despite its frequency, relatively little is known about the prevalence and assessment of dyspnea in general populations. The aims of this review were: 1) to estimate the prevalence of dyspnea in general adult populations; 2) to identify associated factors; and 3) to identify used methods for dyspnea assessment. METHODS: A systematic literature search was conducted using MEDLINE/PubMed, Embase, CINAHL and JAMA network. Records were screened by two independent reviewers and quality was assessed by using the Joanna Briggs Institute checklist for risk of bias in prevalence studies. Multi-level meta-analysis was performed to estimate pooled prevalence. The protocol was registered on PROSPERO (CRD42021275499). RESULTS: Twenty original articles, all from studies in high-income countries, met the criteria for inclusion. Overall, their quality was good. Pooled prevalence of dyspnea in general adult populations based on 11 studies was 10% (95% CI 7, 15), but heterogeneity across studies was high. The most frequently reported risk factors were increasing age, female sex, higher BMI and respiratory or cardiac disease. The MRC or the modified MRC scale was the most used tool to assess dyspnea in general populations. CONCLUSIONS: Dyspnea is a common symptom in adults in high-income countries. However, the high heterogeneity across studies and the lack of data from low- and middle-income countries limit the generalizability of our findings. Therefore, more research is needed to unveil the prevalence of dyspnea and its main risk factors in general populations around the world.

Downregulation of epithelial DUOX1 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by small airway remodeling and alveolar emphysema due to environmental stresses such as cigarette smoking (CS). Oxidative stress is commonly implicated in COPD pathology, but recent findings suggest that one oxidant-producing NADPH oxidase homolog, dual oxidase 1 (DUOX1), is downregulated in the airways of patients with COPD. We evaluated lung tissue sections from patients with COPD for small airway epithelial DUOX1 protein expression, in association with measures of lung function and small airway and alveolar remodeling. We also addressed the impact of DUOX1 for lung tissue remodeling in mouse models of COPD. Small airway DUOX1 levels were decreased in advanced COPD and correlated with loss of lung function and markers of emphysema and remodeling. Similarly, DUOX1 downregulation in correlation with extracellular matrix remodeling was observed in a genetic model of COPD, transgenic SPC-TNF-α mice. Finally, development of subepithelial airway fibrosis in mice due to exposure to the CS-component acrolein, or alveolar emphysema induced by administration of elastase, were in both cases exacerbated in Duox1-deficient mice. Collectively, our studies highlight that downregulation of DUOX1 may be a contributing feature of COPD pathogenesis, likely related to impaired DUOX1-mediated innate injury responses involved in epithelial homeostasis.

An update on pulmonary rehabilitation techniques for patients with chronic obstructive pulmonary disease.

Introduction: Pulmonary rehabilitation (PR) is one of the core components in the management of patients with chronic obstructive pulmonary disease (COPD). In order to achieve the maximal level of independence, autonomy, and functioning of the patient, targeted therapies and interventions based on the identification of physical, emotional and social traits need to be provided by a dedicated, interdisciplinary PR team.Areas covered: The review discusses cardiopulmonary exercise testing in the selection of different modes of training modalities. Neuromuscular electrical stimulation as well as gait assessment and training are discussed as well as add-on therapies as oxygen, noninvasive ventilator support or endoscopic lung volume reduction in selected patients. The potentials of pulsed inhaled nitric oxide in patients with underlying pulmonary hypertension is explored as well as nutritional support. The impact of sleep quality on outcomes of PR is reviewed.Expert opinion: Individualized, comprehensive intervention based on thorough assessment of physical, emotional, and social traits in COPD patients forms a continuous challenge for health-care professionals and PR organizations in order to dynamically implement and adapt these strategies based on dynamic, more optimal understanding of underlying pathophysiological mechanisms.

Personalized medicine for patients with COPD: where are we?

Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD.

Wearable Finger Pulse Oximetry for Continuous Oxygen Saturation Measurements During Daily Home Routines of Patients With Chronic Obstructive Pulmonary Disease (COPD) Over One Week: Observational Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients can suffer from low blood oxygen concentrations. Peripheral blood oxygen saturation (SpO2), as assessed by pulse oximetry, is commonly measured during the day using a spot check, or continuously during one or two nights to estimate nocturnal desaturation. Sampling at this frequency may overlook natural fluctuations in SpO2. OBJECTIVE: This study used wearable finger pulse oximeters to continuously measure SpO2 during daily home routines of COPD patients and assess natural SpO2 fluctuations. METHODS: A total of 20 COPD patients wore a WristOx2 pulse oximeter for 1 week to collect continuous SpO2 measurements. A SenseWear Armband simultaneously collected actigraphy measurements to provide contextual information. SpO2 time series were preprocessed and data quality was assessed afterward. Mean SpO2, SpO2 SD, and cumulative time spent with SpO2 below 90% (CT90) were calculated for every (1) day, (2) day in rest, and (3) night to assess SpO2 fluctuations. RESULTS: A high percentage of valid SpO2 data (daytime: 93.27%; nocturnal: 99.31%) could be obtained during a 7-day monitoring period, except during moderate-to-vigorous physical activity (MVPA) (67.86%). Mean nocturnal SpO2 (89.9%, SD 3.4) was lower than mean daytime SpO2 in rest (92.1%, SD 2.9; P<.001). On average, SpO2 in rest ranged over 10.8% (SD 4.4) within one day. Highly varying CT90 values between different nights led to 50% (10/20) of the included patients changing categories between desaturator and nondesaturator over the course of 1 week. CONCLUSIONS: Continuous SpO2 measurements with wearable finger pulse oximeters identified significant SpO2 fluctuations between and within multiple days and nights of patients with COPD. Continuous SpO2 measurements during daily home routines of patients with COPD generally had high amounts of valid data, except for motion artifacts during MVPA. The identified fluctuations can have implications for telemonitoring applications that are based on daily SpO2 spot checks. CT90 values can vary greatly from night to night in patients with a nocturnal mean SpO2 around 90%, indicating that these patients cannot be consistently categorized as desaturators or nondesaturators. We recommend using wearable sensors for continuous SpO2 measurements over longer time periods to determine the clinical relevance of the identified SpO2 fluctuations.

Thoracic Kyphosis on Chest CT Scans Is Associated With Incident Vertebral Fractures in Smokers.

Greater kyphosis angles lead to increased loading on vertebral bodies in computational models. However, results about the relationship between severity of kyphosis and incident vertebral fracture (VF) risk have been conflicting. Therefore, the aim of this study was to evaluate associations between 1) prevalent VFs and severity of kyphosis, and 2) severity of kyphosis and incident VF risk in smokers with or without chronic obstructive pulmonary disease (COPD). Former and current smokers with or without COPD were included. CT scans were made at baseline, 1-year, and 3-year follow-up. VFs were evaluated on superposed sagittal CT reconstructions. Kyphosis was measured as the angle between the lines above T4 and below T9 or T12 . We included 1239 subjects (mean age 61.3 ± 8.0 years, 61.1% male, 80.6% with COPD), of whom 253 (20.4%) had a prevalent VF and 294 (23.7%) an incident VF within 3 years. Presence, number, and severity of prevalent VFs were associated with a greater kyphosis angle. The mean increase in kyphosis angle within 3 years was small but significantly greater in subjects with incident VFs compared with those without (2.2 ± 4.1 versus 1.2 ± 3.9 degrees, respectively, for T4 to T12 angle, p < 0.001). After adjustment for bone attenuation (BA) and prevalent VFs, baseline kyphosis angle was associated with incident VFs within 1 and 3 years (angle T4 to T12 per +1 SD, hazard ratio [HR] = 1.34 [1.12-1.61] and HR 1.29 [1.15-1.45], respectively). Our data showed that a greater kyphosis angle at baseline was independently associated with increased risk of incident VFs within 1 and 3 years, supporting the theory that greater kyphosis angle contributes to higher biomechanical loads in the spine. © 2019 American Society for Bone and Mineral Research.

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale.

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration.

High Imminent Vertebral Fracture Risk in Subjects With COPD With a Prevalent or Incident Vertebral Fracture.

Subjects with chronic obstructive pulmonary disease (COPD) have an increased risk of vertebral fractures (VFs); however, VF incidence is largely unknown. Therefore, the aim of our study was to determine the incidence of new and/or worsening VF in subjects with COPD. Smokers and subjects with COPD (GOLD II-IV) from the ECLIPSE study with complete set of chest CT scans (baseline and 1- and 3-year follow-up) to evaluate vertebrae T1 down to L1 were included. If a VF was diagnosed on the last scan, detailed VF assessment of the previous scans was performed. VFs were scored according to the method of Genant as mild, moderate, or severe. Main outcome measure was the cumulative incidence of new and/or worsening VF at subject level, within 1 and 3 years. Of 1239 subjects (mean age 61 years, 757 males [61%], 999 subjects with COPD), 253 (20.5%) had ≥1 prevalent VF. The cumulative incidence of VFs was 10.1% within 1 year and 24.0% within 3 years. After adjustment for age, sex, body mass index (BMI), pack-years, and smoking status, prevalence and incidence were similar between smokers and COPD GOLD stages. Within 1 year, 29.2% of the subjects with a prevalent VF had an incident VF, compared with 5.1% in absence of prevalent VF (hazard ratio [HR] = 5.1; 95% confidence interval [CI] 3.6-7.4) and 58.5% versus 15.0% within 3 years (HR = 3.6; 95% CI 2.9-4.6). The incidence of VF was higher with increasing number and severity of prevalent VFs. Among subjects having an incident VF within the first year, 57.3% had a subsequent VF within the next 2 years. In this study, more than half of the smokers and subjects with COPD with a prevalent VF or an incident VF within the first year sustained a subsequent VF within 3 years. The 3-year risk was even higher in the presence of multiple or severe prevalent VFs. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Inhalation therapy for repairing damaged elastin fibers and decelerating elastinolysis in chronic obstructive pulmonary disease.

INTRODUCTION: Current pharmacologic therapy of chronic obstructive pulmonary disease (COPD) can reduce respiratory symptoms and exacerbation frequency. However, no single COPD intervention except for lung transplantation has proven effective in recovering lung function. Lung elasticity is reduced in COPD lungs, which is for a large part due to chronically enhanced elastin degradation. Elastin calcification and formation of advanced glycation end products (AGEs) may also contribute to this. Areas covered: We propose inhalation therapy to induce repair of damaged pulmonary elastin fibers by stimulating tropoelastin synthesis, assembly and crosslinking in order to improve lung function in patients with COPD. Decelerating elastinolysis is another treatment objective, as well as decalcification and deglycation of the extracellular matrix. Expert commentary: Studies should be conducted to test whether it is feasible to restore pulmonary elastin fibers with inhalation therapy. We expect that the optimal formulation will turn out to be a combination of copper, epigallocatechin-(3-)gallate or pentagalloyl glucose, vitamin A/D/K, magnesium, heparin or heparan sulfate, minoxidil and one or more AGEs inhibitors. Establishing a treatment that has the proven ability to facilitate regain of lost lung function in COPD patients would cause a major paradigm shift in this debilitating disease.

Should vitamin K be supplemented instead of antagonised in patients with idiopathic pulmonary fibrosis?

INTRODUCTION: There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF. Areas covered: We advance the hypothesis that modulation of vitamin K-dependent MGP activation in IPF patients by either vitamin K antagonism or administration may result in acceleration and deceleration of fibrosis progression, respectively. Furthermore, shortfall in vitamin K could be suspected in IPF based on the high prevalence of certain co-morbidities, such as vascular calcification and lung cancer. Expert commentary: We hypothesize that vitamin K status is reduced in IPF patients. This, in combination with studies suggesting that vitamin K may play a role in lung fibrosis pathogenesis, would provide a rationale for conducting a clinical trial assessing the potential mitigating effects of vitamin K administration on progression of lung fibrosis, prevention of co-morbidities and mortality in IPF.

The patient with a complex chronic respiratory disease: a specialist of his own life?

INTRODUCTION: The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

Risk of community-acquired pneumonia in chronic obstructive pulmonary disease stratified by smoking status: a population-based cohort study in the United Kingdom.

BACKGROUND: Smoking increases the risk of community-acquired pneumonia (CAP) and is associated with the development of COPD. Until now, it is unclear whether CAP in COPD is due to smoking-related effects, or due to COPD pathophysiology itself. OBJECTIVE: To evaluate the association between COPD and CAP by smoking status. METHODS: In total, 62,621 COPD and 191,654 control subjects, matched by year of birth, gender and primary care practice, were extracted from the Clinical Practice Research Datalink (2005-2014). Incidence rates (IRs) were estimated by dividing the total number of CAP cases by the cumulative person-time at risk. Time-varying Cox proportional hazard models were used to estimate the hazard ratios (HRs) for CAP in COPD patients versus controls. HRs of CAP by smoking status were calculated by stratified analyses in COPD patients versus controls and within both subgroups with never smoking as reference. RESULTS: IRs of CAP in COPD patients (32.00/1,000 person-years) and controls (6.75/1,000 person-years) increased with age and female gender. The risk of CAP in COPD patients was higher than in controls (HR 4.51, 95% CI: 4.27-4.77). Current smoking COPD patients had comparable CAP risk (HR 0.92, 95% CI: 0.82-1.02) as never smoking COPD patients (reference), whereas current smoking controls had a higher risk (HR 1.23, 95% CI: 1.13-1.34) compared to never smoking controls. CONCLUSION: COPD patients have a fourfold increased risk to develop CAP, independent of smoking status. Identification of factors related with the increased risk of CAP in COPD is warranted, in order to improve the management of patients at risk.

Ectopic fat accumulation in patients with COPD: an ECLIPSE substudy.

BACKGROUND: Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities. METHODS: Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2-L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT. A dose-response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran-Armitage trend test. Regression models were used to investigate possible relationships between CT body composition indices and comorbidities. RESULTS: From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2-L3 to assess body composition. CSA of VAT was increased (P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD (P<0.002). Progressively increasing CSA of VAT was not associated with adverse clinical outcomes. The probability of exhibiting low 6MWD and accelerated FEV1 decline increased with progressively decreasing MT attenuation and CSA of MT. In COPD, the probability of having diabetes (P=0.024) and gastroesophageal reflux (P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities (P=0.042). Body composition parameters did not correlate with coronary artery scores or with survival. CONCLUSION: Ectopic fat accumulation is increased in COPD, and this was associated with relevant clinical outcomes and comorbidities.

Gender differences in partners of patients with COPD and their perceptions about the patients.

BACKGROUND/OBJECTIVES: Chronic obstructive pulmonary disease (COPD) not only affects patients but also their partners. Gender-related differences in patients with COPD are known, for instance regarding symptoms and quality of life. Yet, research regarding gender differences in partners of patients with COPD has been conducted to a lesser extent, and most research focused on female partners. We aimed to investigate differences between male and female partners of patients with COPD regarding their own characteristics and their perceptions of patients' characteristics. DESIGN: Cross-sectional study. SETTING: Four hospitals in the Netherlands. PARTICIPANTS: One hundred and eighty-eight patient-partner couples were included in this cross-sectional study. MEASUREMENTS: General and clinical characteristics, health status, care dependency, symptoms of anxiety and depression, social support, caregiver burden, and coping styles were assessed during a home visit. RESULTS: Female partners had more symptoms of anxiety and a worse health status than male partners. Social support and caregiver burden were comparable, but coping styles differed between male and female partners. Female partners thought that male patients were less care dependent and had more symptoms of depression, while these gender differences did not exist in patients themselves. CONCLUSION: Health care providers should pay attention to the needs of all partners of patients with COPD, but female partners in particular. Obtaining an extensive overview of the patient-partner couple, including coping styles, health status, symptoms of anxiety, and caregiver burden, is necessary to be able to support the couple as effectively as possible.

Domain-specific cognitive impairment in patients with COPD and control subjects.

Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls.

COPD care delivery pathways in five European Union countries: mapping and health care professionals' perceptions.

BACKGROUND: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. OBJECTIVE: The aim of this study was to compare COPD patients' care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals' (HCPs) perceptions about the current pathways. METHODS: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. RESULTS: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. CONCLUSION: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients' engagement could optimize current care pathways resulting in a better integrated system.

Sputum microbiology predicts health status in COPD.

BACKGROUND: Spontaneous sputum production occurs in a subset of COPD patients; however, its clinical relevance has not been established. Differences in health status and clinical outcomes between patients with and without positive sputum cultures are unknown. OBJECTIVE: To compare clinical characteristics and health status of spontaneous sputum producers with a positive culture (SC+) and negative culture (SC-) with nonsputum producers (NP) in a cohort of COPD patients referred for pulmonary rehabilitation. METHODS: In total, 518 clinically stable patients with mild-to-very severe COPD were recruited (mean age: 64.1±9.1 years, 55.6% males, forced expiratory volume in 1 second 48.6%±20.0% predicted). Health status was measured using COPD Assessment Test, St George's Respiratory Questionnaire, and the Clinical COPD Questionnaire. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Exercise capacity was measured using the 6-minute walking distance. Spontaneously expectorated sputum was cultured for microbiology. RESULTS: Almost one-third of patients spontaneously produced sputum (n=164, 31.7%). Despite comparable lung function, SC+ reported more frequent exacerbations than NP (≥2 exacerbations <1 year: 43 [81.1%] vs 179 [50.6%], P<0.001). COPD Assessment Test total score and the Clinical COPD Questionnaire total score were significantly worse in SC+ than NP (23.9±6.1 vs 21.1±6.7, P=0.012; 3.1±1.0 vs 2.5±1.0, P=0.002; respectively). Hospital Anxiety and Depression Scale-D score was significantly higher in SC+ than NP (8.7±4.1 vs 7.2±4.3, P=0.046). CONCLUSION: Spontaneous sputum production is common in COPD. Particularly, patients with positive cultures have worse health status and more symptoms of depression. Impact on disease progression and long-term outcomes remain to be established. CLINICAL TRIAL REGISTRATION: NTR3416, registered at www.trialregister.nl.

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease.

The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland-Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of -0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis.

Measurement properties of the Timed Up & Go test in patients with COPD.

We aimed to investigate the construct validity of the Timed Up & Go (TUG) test in chronic obstructive pulmonary disease (COPD), to identify characteristics related to an abnormal TUG time and to examine the responsiveness of the TUG to pulmonary rehabilitation (PR). TUG time was assessed before and after comprehensive PR in 500 COPD patients, and compared cross-sectionally in 100 non-COPD subjects. Physical health outcomes, mental health outcomes, symptom-related outcomes and multidimensional indices were assessed in COPD patients only. Good convergent and discriminant validity was demonstrated by fair-to-moderate correlation with physical health outcomes, symptom-related outcomes and multidimensional indices ( rs = 0.18-0.70) and by little correlation with mental health outcomes ( rs = 0.21-0.26). COPD patients had a worse TUG time than non-COPD subjects, demonstrating known-groups validity. A TUG time of 11.2 seconds had good sensitivity (0.75) and specificity (0.83) for identifying patients with a baseline 6-minute walk distance <350 m. TUG time improved after PR ( p < 0.0001) and a change of 0.9-1.4 seconds was identified as clinically important. The TUG is valid and responsive in COPD. An abnormal result is indicative of poor health outcomes. This simple test provides valuable information and can be adopted in clinical and research settings.

Barriers and facilitators to end-of-life communication in advanced chronic organ failure.

AIM: The aim of this quantitative, cross-sectional study was to identify barriers and facilitators to end-of-life communication experienced by family caregivers of patients with advanced chronic organ failure and to examine agreement in barriers and facilitators between family caregivers and patients. METHODS: Patients and family caregivers were interviewed using the barriers and facilitators questionnaire. Agreement was determined using intraclass correlation coefficients for continuous variables and Cohen's kappa for categorical variables. RESULTS: A total of 158 patients and family caregiver dyads were included. The most important barriers for family caregivers were related to uncertainty about expected care and focus on staying alive instead of dying. The facilitators were related to trust in and competence of their physician and earlier experiences with death in their (social) environment. For most barriers and facilitators, agreement between patients and family caregivers was fair to moderate. CONCLUSION: Differences in barriers and facilitators between patients and family caregivers ask for an individual approach to facilitate end-of-life communication.