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PAM PATTON SENIOR RESPIRATORY NURSE HINCHINGBROOKE HOSPITAL AIMS OF THE SESSION Look at COPD as not just a Lung disease Look at the development of systemic consequences and common co-morbidities Look at possible mechanisms by which they develop What is COPD? A disease state characterised by airflow limitation that is not fully reversible and is usually progressive Associated with an enhanced chronic inflammatory response in the airways and the lungs to noxious particles or gases Predicted to be 3rd leading cause of death worldwide by 2020 Treatable but not curable Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update NICE guidelines [CG101] Published date: June 2010 COPD definition - GOLD Most recent update by Global Initiative for COPD (GOLD) 2015 defines COPD as “ a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the symptom characterised by airflow limitation that is not fully reversible” Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015. We know that Cigarette smoking is the commonest cause of COPD Only a percentage of smokers(so called susceptible smokers) develop the disease (approx 25%) 20% patients are non smokers Developing COPD: a 25 year follow up study of the general population Thorax2006;61:935-939 doi:10.1136/thx.2006.062802 Cigarette smoke Cigarette associated noxious agents injure the airway epithelium and drive the key process that leads to specific airway inflammation So if we remove the agent, repair process should bring the airways back to their normal structure But!!! However This inflammatory response is enhanced and fails to resolve after quitting smoking in patients who develop COPD Switch from a self limiting inflammation to chronic persistent inflammation This clearly indicates that the regulation of the inflammatory response is abnormal This inflammatory process contributes to remodelling of pulmonary tissue Rennard S I Inflammation in COPD : a link to systemic comorbidities European Respiratory Review 1 September 2007 What we do know COPD is associated with clinically significant systemic alterations in biochemistry and organ function Altered circulating levels of inflammatory mediators and acute-phase proteins (CRP) rise with severity of COPD Altered levels of several cytokines such as interleukin-1 and tumour necrosis factor alpha (TNFα) Oxidative stress is over activated in COPD causing tissue damage Stockley RA, Systemic inflammation and comorbidity in COPD: a result of overspill of inflammatory mediators from the lungs? Thorax 2010;65 930-936 So although the Ventilatory system is clearly dysfunctional Inflammatory mediators generated in the lung enter the blood stream and may have systemic effects on other susceptible areas of the body Nussabaumer-Ochsner Y, Rabe KF Syestemic manifestations of COPD. Chest 2011 Jan;139(1) 165-73 Systemic effects and Mortality Can seriously affect quality of life Worsen clinical prognosis Some common co- morbidities include Skeletal muscle dysfunction Weight loss Cardiovascular disease Diabetes Osteoporosis Anxiety/Depression Hypertension Lung Cancer Pulmonary hypertension Cor Pulmonale Sleep Apnoea GORD Anaemia Skeletal Muscle Dysfunction (SMD) SMD Lower muscle strength Lower muscle endurance Sarcopenia (loss of muscle cells) and abnormal function of remaining cells Together called “skeletal muscle dysfunction” SMD Exercise limitation has traditionally been explained by the increased work of breathing and dynamic hyperinflation However SMD is often a very significant contributor in these patients Each muscle is made up of millions of fibers In COPD these fibers can become smaller, weaker and may even waste away entirely Some research suggests this is part of the systemic inflammatory process that weakens and damages muscles over time Hypoxia Low oxygen levels over time decreases the size of muscle fibers Leads to muscle weakness Muscle symptoms - multifactorial Inactivity Poor diet Inflammation muscle fatigue – exercise intolerance Poor health status Weight loss in COPD Weight loss in COPD Studies of body composition in COPD show that both fat mass and fat-free mass are lost. Increased breakdown of muscle proteins , a typical feature of cachexia, has been demonstrated in patients with COPD Poor prognostic factor Causes Less interest in food difficulty swallowing or chewing due to dysponea Full stomach Using more energy and nutrients – more energy to breathe or do any physical activity Steroids – breaks down muscle tissue Weight loss cont’d chronic mouth breathing, which can alter the taste of food chronic mucous production coughing; fatigue; depression side effects of medications. NICE Guidelines on Nutritional Factors 1.2.12.6 BMI should be calculated in patients with COPD: the normal range for BMI is 20 to less than 25[8] if the BMI is abnormal (high or low), or changing over time, the patient should be referred for dietetic advice if the BMI is low patients should also be given nutritional supplements to increase their total calorific intake Be encouraged to take exercise (anobolic stimulus) to augment the effects of nutritional supplementation. 1.2.12.7 Refer to 'Nutrition support in adults' (NICE clinical guideline 32). [2004] Combination of the 2 Muscle Weakness weight loss Muscle weakness with weight loss Body breaks down muscle and makes the patient weaker Leads to more shortness of breath and less activity Leads to weaker muscles Cycle of deconditioning Patients who are breathless avoid exercise and other physical activities that make them sob Muscles start to lose strength and endurance Can be difficult to break the cycle Pulmonary rehabilitation Goals To reduce symptoms disability handicap improve their quality of life Pulmonary rehabilitation Positive outcomes include: a reduction in exacerbations improved prognosis improved quality of life Cardiovascular disease in COPD Cardiovascular disease Evidence has shown that COPD is associated with cardiovascular risk As FEV1 fell increase in the arterial wall stiffness was found Patients with severe airflow obstruction more likely to have electrocardiogram evidence of ischemic heart disease compared to no airflow obstruction Targeted treatment in COPD: a multi-system approach for a multi-system disease. Anderson D1, Macnee W. Int J Chronic obstructive Pulmonary Dis 2009;4:321-35. Epub 2009 Sep 1. So Is the systemic inflammation as a result of COPD causing vascular endothelial damage? Higher levels of systemic inflammation were found in COPD patients with evidence of IHD COPD Inflammation Can Contribute to Cardiovascular Disease Lung Inflammation Acute Chronic TNF-α C-reactive Protein Autonomic Instability IL-6 GM-CSF Fibrinogen Neutrophils Arrhythmias Coagulation Progressive Atherosclerosi GM-CSF = granulocyte-macrophage colony stimulating factor s IL = interleukin TNF = tumor necrosis factor Rennard SI. Proc Am Thorac Soc. 2005;2:94-100. Permission requested. Inflammation Diabetes in COPD Risk factors Risk appears to exist regardless of the severity of COPD • An increase in body mass index (BMI) • Inflammation Oral corticosteroids Inhaled corticosteroids Chicken and egg – which came first? Some of the same inflammatory markers are increased in diabetes and COPD Inflammation may induce insulin resistance by blocking signalling through the insulin receptor and increase the risk of type 2 diabetes High glucose levels Elevated levels of blood glucose are associated with abnormal lung function. loss of respiratory compliance (ability of the lungs to distend) associated with diabetes weakened respiratory muscles can cause a reduction in the ability of the lung tissue to transfer oxygen (diffusing capacity) Goldman MD Lung Dysfunction in Diabetes. Diabetes Care June 2003 Vol 26 no 6 1915-1918 Osteoprosis Often overlooked and undertreated Clinically a silent disease until it manifests in the form of a pathological fracture Primary focus is to improve and maintain lung function Don’t realise patients have low bone mass Increased risk factors identified: Smoking Increased alcohol intake Low Vitamin D Levels Genetic factors Treatment with corticosteroids Reduced skeletal muscle mass and strength Low BMI Ionescu AA, Schoon E. Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J. 2003;22 (Suppl 46):64s-75s. cont’d Chronic Systemic Inflammation Inflammation exerts significant influence on bone turn over Pro inflammatory cytokines play a critical role in regulating osteoblasts and osteoclasts Ginaldi L, et al Immunity and aging 2005;14-18 Inflammatory Mediators in Osteoporosis IL-1 IL-6 IL-11 TNF- Transforming growth factor (TGF) - Nitric oxide (NO) Receptor activator of NFB (RANK)/RANK ligand (RANKL) Ginaldi L, et al. Immunity and Aging. 2005;2:14-18. Anxiety and Depression Anxiety and depression Depression may not always be recognised Depression is two or three times more common in patients with chronic diseases than in those who have good physical health. NICE Clinical Guideline (October 2009) Risk factors include: Severe dyspnoea Physical disability Long term oxygen therapy Low body mass index FEV1 ≤50% predicted Poor quality of life Presence of comorbidity Living alone Have been seen or admitted to hospital for an exacerbation Maurer J RebbapragadaV, Borson et al. Anxiety and depression in COPD :current understanding, unanswered questions and research needs. Chest. 2008;134 (4suppl) 43S-56S Systemic inflammation in depression Suggested that depression may be influenced by systemic inflammation Higher levels of TNF-α interleukin-6 (IL-6) were found independent of the severity of airflow obstruction. ATS 2013 Hilary Strollo, M.S., a graduate of the University of Pittsburgh School of Health and Rehabilitation Sciences. Key Questions? During the last month have you:1) often been feeling down, depressed or hopeless 2)Have you found little interest or pleasure in doing things 3) Do you feel upset or frightened by your attacks or breathlessness Consider more formal assessment if patients answer yes Hospital Anxiety and Depression Scale (HADS) Patient health questionaire-9 In Conclusion COPD is associated with high levels of systemic inflammation, secondary to pulmonary inflammation Will the development of therapies that target inflammation in the lung reduce the risk for comorbidities Will the medications have the potential to improve survival, function and quality of life Thank you Any questions?