Christopher B. Cooper

COPD as a lung disease with systemic consequences - Clinical impact, mechanisms and potential for early intervention

The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and co-morbidities. These may be major features in the clinical presentation of COPD, prompting increasing interest. Systemic consequences may be defined as non-pulmonary manifestations of COPD with an immediate cause-and-effect relationship, whereas co-morbidities are diseases associated with COPD. The major systemic consequences/co-morbidities now recognized are: deconditioning, exercise intolerance, skeletal muscle dysfunction, osteoporosis, metabolic impact, anxiety and depression, cardiovascular disease, and mortality. The mechanisms by which these develop are unclear. Probably many factors are involved. Two appear of paramount importance: systemic inflammation, which presents in some patients with stable disease and virtually all patients during exacerbations, and inactivity, which may be a key link to most COPD-related co-morbidities. Further studies are required to determine the role of inflammatory cells/mediators involved in systemic inflammatory processes in causing co-morbidities; the link between activity and co-morbidities; and how COPD therapy may affect activity. Both key mechanisms appear to be influenced significantly by COPD exacerbations. Importantly, although the prevalence of systemic consequences increases with increasing severity of airflow obstruction, both systemic consequences and co-morbidities are already present in the Global Initiative for Chronic Obstructive Lung Disease Stage II. This supports the concept of early intervention in chronic obstructive pulmonary disease. Although at present early intervention studies in COPD are lacking, circumstantial evidence suggests that current treatments may influence events leading to the systemic consequences and co-morbidities, and thus may affect the clinical manifestations of the disease.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement highlighting research areas that will have the greatest impact on patient-centred outcomes in COPD http://ow.ly/LXW2J

Exercise in chronic pulmonary disease: aerobic exercise prescription.

Endurance exercise training (EXT) is singly the most important aspect of rehabilitation for patients with chronic pulmonary disease. When effective, this modality of physical reconditioning leads to improved functional exercise capacity and reduced breathlessness. Early implementation is desirable to obtain more meaningful responses (e.g., when FEV1 falls below 50% of the predicted value in patients with chronic obstructive disease). Preparation for effective EXT requires optimization of respiratory system mechanics (e.g., using bronchodilator therapy), prevention of gas exchange failure (i.e., using supplemental oxygen), nutritional guidance, and psychological support (e.g., to overcome stigmata of disability, fear, and inclination to panic). EXT should be applied using a rigorous, scientifically based aerobic exercise prescription (AXRx) that recognizes basic principles of the human response to exercise prescription while considering individual pathophysiological limitations and identifying safety thresholds for exercise participation. The mode of aerobic exercise should use large muscle groups of the legs (e.g., treadmill or cycle ergometer). The recommended duration is an accumulation of 30 min of exercise per session at the target intensity, achieved by continuous or interval training. EXT should be supervised with a recommended frequency of at least three times per week for 6--8 wk. Target exercise intensity can be monitored by oxygen uptake, work rate, heart rate, or perceived exertion. Target intensity can be determined initially on the basis of 40% of a reference value for maximum oxygen uptake and linked to other variables through predictable interrelationships. All aspects of the AXRx must be reviewed with regard to progression during training. Pulmonary rehabilitation must recognize the importance of achieving clinically meaningful responses (e.g., increased 6-min walking distance of 54 m) as well as the need for maintenance exercise program to sustain the benefits.

Treatment of COPD: the sooner the better?

Classical belief is that only smoking cessation, and not pharmacotherapy, beneficially affect disease progression in chronic obstructive pulmonary disease (COPD). In recent years, new data on pharmacotherapy of COPD became available that shed new light on this question. The present paper reviews these data critically in an attempt to put them in a proper perspective. The most impressive new data are subgroup analyses of two large-scale long-term trials. With these new data it is now clear that patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) stage II benefit as much from pharmacotherapy as patients in the later stages of the disease. Effects on prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV1), health-related quality of life, exacerbations and hospitalisations appear at least as pronounced in GOLD stage II as in the other GOLD stages. In addition, evidence suggestive of an effect on disease progression is available in the sense of an effect on rate of decline of FEV1, and trends for reductions in mortality. Finally, good evidence is available that, in contrast to conventional thinking, decline of FEV1 occurs at a considerably faster rate in the early stages of the disease. These data together with the high prevalence of co-morbidities from early in the disease onwards provide us with strong suggestive evidence for early intensive intervention in COPD. New trials, particularly demonstrating the detrimental effects of delaying treatment until later in the course of the disease, are required to render the evidence for early intensive intervention irrefutable.

An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. METHODS Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified. RESULTS Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. CONCLUSIONS Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.

Effect of a collaborative weaning plan on patient outcome in the critical care setting

ObjectiveThe process of weaning from mechanical ventilation can be complex, requiring collaborative care planning by members of the healthcare team. Improved outcomes have been demonstrated to result from collaborative decision-making processes (e.g., when ventilator teams were utilized). The purpose of this study was to evaluate the effect of a collaborative weaning plan (CWP) on length of time on mechanical ventilation, length of stay in the intensive care unit (ICU), and cost. DesignA new, collaborative weaning plan in the form of a weaning board and flowsheet was introduced into a medical intensive care unit (MICU) setting. A pre- and post-quasi-experimental design using historical controls was used to test the hypotheses. Attempts to control for the effects of history were made by collecting data related to patient, staffing, and organizational variables that could independently effect outcome. SettingMICU in a west coast teaching hospital. PatientsCritically ill patients receiving mechanical ventilation for 3 days or greater. InterventionImplementation of a collaborative weaning plan. MeasurementsOutcomes studied included length of stay in the MICU, length of time patients were mechanically ventilated in the MICU, cost per MICU stay, and the incidence of complications (e.g., reventilation, readmission to the ICU, and mortality rate.) Main ResultsThe CWP decreased length of stay in the MICU by 3.6 days (p = .03) and length of ventilator time by 2.7 days (p = .06). There were no significant differences between groups related to cost or incidence of complications. ConclusionsThese results support the usefulness of collaborative structures (such as weaning boards/flowsheets) in decreasing ICU length of stay.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement: which types of research will have the greatest future impact on patient-centred outcomes in COPD? http://ow.ly/I54Hb

Airflow obstruction and exercise

The primary abnormality in chronic obstructive pulmonary disease (COPD) is chronic airway inflammation which results in airflow limitation. Disease progression is usually depicted as an accelerated decline in FEV(1) over time. However, COPD patients also manifest progressive static hyperinflation due to the combined effects of reduced lung elastic recoil and increased airway resistance. Superimposed on static hyperinflation are further increases in operational lung volumes (dynamic hyperinflation) brought on during exercise, exacerbations or tachypnea. An important consequence of exertional dyspnea is activity limitation. COPD patients have been shown to spend only a third of the day walking or standing compared with age-matched healthy individuals who spend more than half of their time in these activities. Furthermore, the degree of activity limitation measured by an accelerometer worsens with disease progression. COPD patients have been shown to have an accelerated loss of aerobic capacity (VO(2)max) and this correlates with mortality just as is seen with hypertension, diabetes and obesity. Thus physical inactivity is an important therapeutic target in COPD. Summarizing; airflow obstruction leads to progressive hyperinflation, activity limitation, physical deconditioning and other comorbidities that characterize the COPD phenotype. Targeting the airflow obstruction with long-acting bronchodilator therapy in conjunction with a supervised exercise prescription is currently the most effective therapeutic intervention in earlier COPD. Other important manifestations of skeletal muscle dysfunction include muscle atrophy and weakness. These specific problems are best addressed with resistance training with consideration of anabolic supplementation.

Improvement in self-reported exercise participation with the combination of tiotropium and rehabilitative exercise training in COPD patients

Background Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation. We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation. Methods COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily (tiotropium = 47, placebo = 44). Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation. Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit. Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis. For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration. Results Patients (n = 46) had mean age of 67 years, mean baseline FEV1 of 0.84 L (33% predicted). Mean (SE) increase in duration of activities (minutes during 2 weeks prior to each visit) from week 4 (prior to PR) to week 13 (end of PR) was 145 (84) minutes with tiotropium and 66 (96) minutes with placebo. The increase from week 4 to week 25 (end of follow-up) was 262 (96) and 60 (93) minutes for the respective groups. Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium. No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant. Conclusions Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities.

A randomised trial of lung sealant versus medical therapy for advanced emphysema

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. Emphysematous lung sealant therapy is highly efficacious in some patients, but benefits bring significant risks http://ow.ly/JJ2vg