COPD, NICE and the National Clinical Strategy Harold Hosker Airedale Hospital March 2010 Inflammation • COPD is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases • Chronic inflammation is caused by increased numbers of activated inflammatory cells, specifically neutrophils, which can damage lung structure and lead to mucosal oedema and airway narrowing The impact of COPD • More than 30,000 deaths annually in the UK • UK – 900,000 diagnosed patients • Allowing for underdiagnosis, the true number of patients with COPD in England and Wales is likely to be around 1.5 million • Currently the fifth greatest cause of mortality worldwide – over 2.5 million deaths in 2000 • By 2020, COPD will be the third leading cause of mortality • Exacerbations have an impact on patient quality of life and can be life-threatening The typical COPD patient – Generally over 40 years – A smoker or ex-smoker – Presentation with: » cough » excessive sputum production » shortness of breath / wheeze COPD is a heterogeneous disease • Spectrum of clinical disease from ‘pink puffer’ to ‘blue bloater’ • Several different pathological processes Inflammatory mechanisms in COPD Cigarette smoke ? CD8+ lymphocyte Alveolar macrophage Neutrophil chemotatic factors, cytokines (IL-8) mediators (LTB4) Neutrophil Protease inhibitors 1-antitrypsin - Neutrophil elastase Proteases Alveolar wall destruction (emphysema) mucus hypersecretion (chronic bronchitis) What is Spirometry? Spirometry is a method of assessing lung function by measuring the volume of air the patient can expel from the lungs after a maximal expiration. Why Perform Spirometry? • Measure airflow obstruction to help make a definitive diagnosis of COPD • Confirm presence of airway obstruction • Assess severity of airflow obstruction in COPD • Detect airflow obstruction in smokers who may have few or no symptoms • Monitor disease progression in COPD • Assess one aspect of response to therapy • Assess prognosis (FEV1) in COPD • Perform pre-operative assessment Spirometry – Additional Uses • Make a diagnosis and assess severity in a range of other respiratory conditions (eg ILD, MND, G-B) • Distinguish between obstruction and restriction as causes of breathlessness • Screen workforces in occupational environments • Assess fitness to dive • Perform pre-employment screening in certain professions Types of Spirometers • Bellows spirometers: Measure volume; mainly in lung function units • Electronic desk top spirometers: Measure flow and volume with real time display • Small hand-held spirometers: Inexpensive and quick to use but no print out Volume Measuring Spirometer Flow Measuring Spirometer Small Hand-held Spirometers Lung Volume Terminology Inspiratory reserve volume Total lung capacity Inspiratory capacity Tidal volume Expiratory reserve volume Residual volume Vital capacity Standard Spirometric Indices • FEV1 - Forced expiratory volume in one second: The volume of air expired in the first second of the blow • FVC - Forced vital capacity: The total volume of air that can be forcibly exhaled in one breath • FEV1/FVC ratio: The fraction of air exhaled in the first second relative to the total volume exhaled • VC - Vital capacity: A volume of a full breath exhaled in the patient’s own time and not forced. Often slightly greater than the FVC, particularly in COPD Normal Trace Showing FEV1 and FVC FVC Volume, liters 5 4 FEV1 = 4L 3 FVC = 5L 2 FEV1/FVC = 0.8 1 1 2 3 4 5 Time, seconds 6 Spirogram Patterns • Normal • Obstructive • Restrictive • Mixed Obstructive and Restrictive Predicted Normal Values Affected by: Age Height Sex Ethnic Origin Criteria for Normal Post-bronchodilator Spirometry • FEV1: % predicted > 80% • FVC: % predicted > 80% • FEV1/FVC: > 0.7 Spirometry: Obstructive Disease Volume, liters 5 4 Normal 3 FEV1 = 1.8L 2 FVC = 3.2L 1 FEV1/FVC = 0.56 1 2 3 4 5 Time, seconds 6 Obstructive Diseases Associated With Airflow Obstruction • • • • • • • COPD Asthma Bronchiectasis Cystic Fibrosis Sarcoidosis Lung cancer (greater risk in COPD) Obliterative Bronchiolitis Spirometry: Restrictive Disease Normal Volume, liters 5 4 3 Restrictive 2 FEV1 = 1.9L FVC = 2.0L 1 FEV1/FVC = 0.95 1 2 3 4 5 Time, seconds 6 Diseases Associated with a Restrictive Defect Pulmonary • Fibrosing lung diseases • Pneumoconioses • Pulmonary edema • Parenchymal lung tumors • Lobectomy or pneumonectomy Extrapulmonary • Thoracic cage deformity • Obesity • Pregnancy • Neuromuscular disorders • Fibrothorax Spirometry • In COPD and asthma, spirometry is preferred to peak flow (PEFR) readings • Serial PEFR readings can confirm / exclude variability (asthma) • Chest X-ray excludes other pathologies but does not usually diagnose COPD Flow Volume Curve • Standard on most desk-top spirometers • Adds more information than volume time curve • Less understood but not too difficult to interpret • Better at demonstrating mild airflow obstruction Flow Volume Curve Maximum expiratory flow (PEF) Expiratory flow rate L/sec TLC FVC Inspiratory flow rate L/sec Volume (L) RV COPD - dynamic hyperinflation COPD - exertional dyspnoea Flow volume loop - severe COPD Flow (l/s) 12 Predicted Baseline Post BD 10 8 6 4 2 2 -2 -4 -6 -8 4 6 8 Volume (litres) Flow volume loop - asthma Flow (l/s) 12 Predicted Baseline Post BD 10 8 6 4 2 2 -2 -4 -6 -8 4 6 8 Volume (litres) Flow volume loop - restrictive (fibrosis) Flow (l/s) 12 Predicted Baseline Post BD 10 8 6 4 2 2 -2 -4 -6 -8 4 6 8 Volume (litres) Flow volume loop - large airways obstruction (stridor) Flow (l/s) 12 Predicted Baseline Post BD 10 8 6 4 2 2 -2 -4 -6 -8 4 6 8 Volume (litres) Bronchodilator Reversibility Testing • Provides the best achievable FEV1 (and FVC) • Helps to differentiate COPD from asthma Must be interpreted with clinical history neither asthma nor COPD are diagnosed on spirometry alone Bronchodilator Reversibility Testing in COPD Results •An increase in FEV1 that is both greater than 200 ml and 12% above the prebronchodilator FEV1 (baseline value) is considered significant •It is usually helpful to report the absolute change (in ml) as well as the % change from baseline to set the improvement in a clinical context Equipment Maintenance • Most spirometers need regular calibration to check accuracy • Calibration is normally performed with a 3 litre syringe • Some electronic spirometers do not require daily/weekly calibration • Good equipment cleanliness and anti-infection control are important; check instruction manual • Spirometers should be regularly serviced; check manufacturer’s recommendations Other lung function tests • Lung volumes – Helium dilution, body box (plethysmography) – TLC (RV derived) • Gas transfer – Single breath carbon monoxide transfer – TLCO and KCO (=TLCO/Va) • Mouth pressures – Indirect measure of muscle / diaphragm strength – Pimax, PEmax Emphysema - the ‘pink puffer’ Damage to alveoli in emphysema Effect of cigarette smoke on airspaces in mice (scanning EM) A: smoke-exposed mice B: matched controls (6 months) Pathological processes in emphysema • Loss of alveolar surface area • Loss of lung elasticity • Hyperinflation causing mechanical inefficiency • Muscle weakness / cachexia • Small airways collapse • Dynamic hyperinflation Alveolar wall damage leading to small airways collapse in COPD Chronic bronchitis: the ‘blue bloater’ Pathological processes in chronic bronchitis • • • • • • • • Bronchoconstriction Airway mucosal inflammation / oedema Airway remodelling / fibrosis Mucus hypersecretion Epithelial / ciliary dysfunction Ventilation - perfusion mismatch Hypoxic pulmonary vasoconstriction Cor pumonale The role of exacerbations in disease progression • Following an exacerbation, the likelihood of further exacerbation increases • Exacerbations are closely associated with cumulative reduction in health status • High frequency of COPD exacerbations is associated with a rapid decline in lung function and increased risk of hospitalisation • Up to 70% of patients admitted to hospital with an exacerbation are re-admitted within a year COPD Guidelines • The British Thoracic Society (BTS) guidelines for the management of COPD 1997 • Global Strategy for the Diagnosis, Management and Prevention of COPD (GOLD), last update in 2001 and are constantly under peer review (www.goldcopd.com) • NICE guidelines were published in 2004, due for revision 2010 1. COPD Guidelines Group of the Standards of Care Committee of the BTS. 1997. 2. Pauwels RA et al. 2001. NICE/BTS Recommendations • Diagnose COPD • Stop Smoking • Effective inhaled therapy • Pulmonary Rehabilitation • NIV • Manage exacerbations • Multi-disciplinary working Inhaled steroids in COPD – No evidence of benefit in mild / moderate COPD – Do not affect the rate of decline in FEV1 – Beneficial effect on quality of life and exacerbation rate in moderate / severe disease – Dose response and long term safety in COPD are not known1 Drug therapy in COPD • Combination therapy – Inhaled steroid plus long-acting B2 agonist – Several studies show additive benefit using fluticasone / salmeterol or budesonide / eformoterol – Benefits include FEV1 change, exacerbation rates, symptom scores and health status improvements – New combinations (including triple combinations and ultra-long acting beta agonists) are on their way – Roflumilast (PDE-4 inhibitor) due 2010 TORCH: study design 3-year study duration (6,112 patients)1 (sub-cut population 4,511 patients2) Full study Sub-cut data SeretideTM 500 Accuhaler™ Fluticasone propionate 500 mcg 2 week run-in Salmeterol 50 mcg Control group 1 Year 1. 2. Vestbo et al. Eur Respir J 2004 GSK Data on File SERTCODOF012 2 Years n=1,533 n=1,117 n=1,534 n=1,126 n=1,521 n=1,142 n=1,524 n=1,126 3 Years All-cause mortality at 3 years Probability of death (%) 18 16 14 12 10 8 6 4 Placebo SALM FP SALM/FP 2 0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Time to death (weeks) Number 1524 alive 1533 1521 1534 1464 1487 1481 1487 1399 1426 1417 1409 Vertical bars are standard errors 1293 1339 1316 1288 Premature study drug discontinuation Probability of withdrawal (%) HR 0.69, p< 0.001 48 44 40 36 32 28 24 20 16 12 8 SFC Control 4 0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Time to withdrawal from study medication (weeks) SFC = salmeterol/fluticasone propionate combination Calverley et al. NEJM 2007 Rate of moderate and severe exacerbations over three years Mean number of exacerbations/year 1.2 1.13 25% reduction 0.97* 1 0.93* 0.85*†‡ 0.8 0.6 0.4 0.2 0 Placebo SALM FP SALM/FP Treatment *p < 0.001 vs placebo; †p = 0.002 vs SALM; ‡p = 0.024 vs FP Calverley et al. NEJM 2007 UPLIFT trial NEJM October 2008 • A 4 year trial of tiotropium in COPD involving 5993 patients • Real life study – all patients allowed to continue all other Rx except inhaled anti-cholinergics • 46% patients were GOLD stage II (FEV1 50% – 80% predicted) ie mild disease • 44% GOLD stage III, 8% GOLD stage IV • 60% patients on LABAs, 62% on ICS, with more than 70% on each by end of trial UPLIFT: rate of decline in lung function Kaplan-Meier Estimates of the Probability of COPD Exacerbation and Death from Any Cause UPLIFT trial exacerbations • 14% reduced risk of exacerbations (time to 1st exacerbation)(p<0.001) and exacerbations leading to hospitalisations (p=0.002) • But no difference in hospital days • Seretide and Tiotropium both reduce exacerbations to a similar extent (INSPIRE study) UPLIFT – safety of Tiotropium • UPLIFT shows no increased risk of cardiac death with Tiotropium (significantly reduced risk – 27% risk reduction in CVS death, also stroke) • 16% risk reduction in probability of death, p=0.034) • No evidence of increased CVS risk from LABAs either Case study – Margaret Margaret is 52 years old. She works in an office and has two children She has smoked around 25 cigarettes a day for 30 years Her FEV1 is 65% predicted Margaret’s father died 4 years ago of ‘chest disease’ She has a productive cough and finds she is breathless on exertion both at work and at leisure Last winter she had a bad chest infection She has tried various inhalers The stages of COPD – NICE Mild (FEV1 50–80%) Moderate (FEV1 30–49%) Breathlessness and exercise limitation Short- and long-acting bronchodilators 2-agonists/anticholinergics If still symptomatic consider a trial of combination long-acting 2-agonist and inhaled corticosteroid* Consider adding theophylline Severe (FEV1 <30%) Prevention of exacerbations If still symptomatic despite maximum inhaled bronchodilator consider referral for specialist assessment 1. NICE Guideline No.12. Thorax 2004. *Discontinue if no benefit after 4 weeks In patients suffering two or more exacerbations per year add inhaled corticosteroid usually in combination with long-acting bronchodilators Case study – Margaret (age 52) Diagnosis Margaret has mild/moderate COPD History Has tried to quit smoking Chest infection last winter Prescribed various inhalers FEV1 = 65% predicted normal Symptoms Breathlessness on exertion getting worse Productive cough What do Margaret’s symptoms stop her doing? Enjoying leisure activities with her family Playing bowls Managing Margaret’s COPD Smoking Breathlessness and exercise limitation Exacerbations QoL Managing Margaret’s COPD Smoking Breathlessness and exercise limitation Exacerbations QoL Managing Margaret’s COPD symptoms Smoking Breathlessness and exercise limitation Exacerbations QoL Further minimising the impact of exacerbations • The impact of exacerbations should be minimised by: – Giving self-management advice on responding promptly to the symptoms of an exacerbation Starting appropriate treatment with oral corticosteroids and/or antibiotics – Use of non-invasive ventilation when indicated – Use of hospital-at-home or assisted-discharge schemes Managing Margaret’s COPD Smoking Breathlessness and exercise limitation Exacerbations QoL Managing Margaret’s COPD • Encourage and help her to stop smoking • Check that Margaret's inhaled therapy is in line with her disease severity and that both symptoms and frequency of exacerbations are taken into consideration. This may involve treatment with LAMAs, and / or LABAs • Check Margaret is able to use and understands the benefit of the treatments she is prescribed • Consider other interventions, e.g. pulmonary rehabilitation • Work with Margaret to develop a selfmanagement plan FEV1 (% of value at age 25) Stopping smoking slows decline in lung function Never smoked or not susceptible to smoke 100 75 Smoked regularly and susceptible to its effects 50 Stopped at 45 Disability 25 Stopped at 65 Death 0 25 50 Age (years) Adapted from: Fletcher et al, Br Med J 1977. 75 Pulmonary rehabilitation • Pulmonary rehabilitation is a multidisciplinary programme of care for patients with COPD and is individually tailored to optimise a patient’s physical and social performance1 • Identify patients who will benefit from pulmonary rehabilitation, usually MRC dyspnoea scale grade 3 or above1 Grade Degree of breathlessness related to activity 1 Not troubled by breathlessness except on strenuous exercise 2 Short of breath when hurrying or walking up a slight hill 3 Walks slower than contemporaries on level ground because of breathlessness or has to stop for breath when walking at own pace 4 Stops for breath after walking about 100m or after a few minutes on level ground 5 Too breathless to leave the house or breathless when dressing or undressing 1. NICE guideline No. 12. Thorax 2004. Recognising an exacerbation • Give written information on recognising worsening symptoms, such as: – You get much more breathless than you did before (doing the same thing) – You produce more sputum than before – Your sputum becomes discoloured – You feel feverish or unwell – Cough gets worse 1. NICE guideline No. 12. Thorax 2004. NICE – inhaler technique • In most cases bronchodilator therapy is best administered using a hand-held inhaler device (including a spacer device or other aid if appropriate) • If the patient is unable to use a particular device satisfactorily or it is not suitable for him/her, an alternative should be found • Inhalers should be prescribed only after patients have received training in the use of the device and have demonstrated satisfactory technique 1. NICE guideline No. 12. Thorax 2004. Case 2 - George • • • • • • • • • 75 year old ex-steel worker Ex-smoker, 45 pack years Chronic productive cough Gradually progressive SOB and wheeze over ten years Regular antibiotics for bronchitis most winters Limited exercise capacity Difficulty shopping, playing with grandkids, walking to pub 15 year history of of ‘asthma’ – bricanyl/beclomethasone No family history of asthma/no pets Points for discussion • Diagnosis • Impact on Patient • What else do you need to know? – What do you need to ask? – Examination? – What investigations do you need? How do we exclude asthma? Spirometry FEV1 = 40% FEV1 /FVC = 50% George • • • • • 75 year old man No night-time wakening No day to day variability in symptoms No acute precipitants No diurnal variation in PEFR Therefore no significant asthmatic element Presentation sponsored by GlaxoSmithKline LM34524 LOM/SLK/06/28416/1 George • • • • • • • • 75 year old man Moderate COPD Enjoyed pulmonary rehabilitation Started combination treatment of ICS and LABA Also on LAMA (tiotropium) Less frequent daily symptoms Less exacerbations requiring antibiotics Better exercise capacity, mild limitation Case 3 - Stanley • • • • 76 yr old man 10yr history of COPD Ex-smoker, (50 pack years) Current Rx – – – – ICS/LABA combination Tiotropium Theophylline Mucolytic Stanley • Housebound – Unable to walk to pub • • • • • Living in sitting room Sleeps in chair Weight loss Declines social services assistance DN noted ankle oedema Points for discussion • FEV1 = 35% • FEV1/FVC = 50% • What else do you need to know? – What would you ask? – Examination? – Investigations? LTOT Assessment • Surgery pulse oximetry – Sats <92% – Measure when COPD stable – repeated after 6 weeks • Or refer for assessment (ABG) National Clinical Strategy for COPD • Started in 2005 (as an ‘NSF’) following pressure from BLF and BTS; originally scheduled for 2007 publication; then 2008; then launch in spring 2009; then winter 2009; now April 2010…….. • Currently the final document being shared with ministers • 12 week consultation from Dec 2009, including workshops nationally • Focus on clinical pathways and managed clinical networks • Now includes asthma and home oxygen services (OSA to follow later) Issues behind the national clinical strategy • COPD is a ‘Cinderella’ disease with little funding or strong advocacy • A lack of awareness of COPD by healthcare professionals and the public • Little focus on prevention and risk reduction • Large numbers of people not diagnosed or inaccurately classified • No clear or uniform care pathways and models of care provision including for acute and chronic care • Varying access to early discharge schemes, pulmonary rehabilitation and supportive care • Access to specialist services at end of life is poor National Clinical Strategy for COPD • Launch end of Q1 2010 • New DH Respiratory Programme Board • Variety of guidance / educational resources etc • Need to reduce: – Variation in care / outcomes – Unnecessary tests / duplication – Ineffective prescribing (25% of oxygen prescriptions are ineffective) National Clinical Strategy for COPD: national structure • National Clinical Leads • Respiratory Leads in each of 10 SHAs • Trust Medical Directors (acute Trusts and PCTs) – Ensure local leadership – Promote local respiratory networks National Clinical Strategy for COPD • Guidelines on diagnostics and case-finding spirometry • Competency framework for HCPs • COPD commissioning guidance • Metrics for primary and secondary care • Tariffs (reduce disincentives) • DH – develop ‘Lung Improvement Programme’ to develop managed lung clinical networks, start national pilots, share information, resources etc ‘Lung Improvement Programme’ Major areas for piloting • Good Lung Health – smoking, case-finding, health checks • Diagnostic Hub – accurate diagnostics for COPD, sleep, asthma, oxygen assessment • Care closer to home – personal health plans • Transforming inpatient care – structured admission, EDS, integrated care, daily respiratory team involvement • End of Life care – care plans, carers, death at home / hospice (60% die in hospital) Oxygen services • Concern re commissioning, implementation and costs of current national oxygen services • Costs £110 M pa • 25% prescriptions – no benefit • 300 NPSA alerts / SUI and 44 oxygen related deaths • Plan to re-commission in 2011 “Well, I guess I’ve taken up enough of your time…..”