Treating Mild COPD Dr Vincent Mak (v.mak@nhs.net) Consultant in Respiratory Integrated Care Imperial College Healthcare Trust, London NHS England (London) Respiratory Network

Disclosures for Dr Vincent Mak Research Support/P.I. No relevant conflicts of interest to declare Employee Consultant Major Stockholder Speakers Bureau Honoraria and support for conference attendance AZ, GSK, Boehringer. Almirall, Novartis, TEVA Chiesi Scientific Advisory Board

What do we mean by “Mild COPD”? Are we talking the same language?

Define Mild COPD - Use Spirometry? GOLD 2014 and NICE (UK) 2010 - FEV1/FVC <0.70 and FEV1 > 80% predicted With or without symptoms Seems fairly simple

Problems with spirometry based diagnosis of Mild COPD Why does FEV1/FVC<0.70 define airflow obstruction? Why not 0.75 or 0.65? Makes COPD a dichotomous disease rather than a continuum. If a heavy smoker with breathlessness has FEV1/FVC 0.70 and FEV1 80% predicted – “by definition” they do not have COPD (and do not fit into any guideline). What if FEV1/FVC=0.69 but FEV1 is >100% predicted? Fixed ratio tends to underdiagnose younger patients and overdiagnose elderly patients When lower limit of normal (LLN) is used rather than fixed ratio, fewer elderly patients are classified as having airflow obstruction So what do they have? Emphysema? Where is the guideline for that?

Fixed FEV1/FVC ratio vs LLN Lamprecht B et al. Pulm Med. 2011;2011:780215. doi: 10.1155/2011/780215

Define Mild COPD using symptoms – is this Mild disease? Any stage GOLD/NICE spirometry with: No self reported symptoms MRC ≤2 (mMRC 1) <1 exacerbation/year

Is Mild COPD same as Early COPD? COPD – “a story with no beginning, a middle that is a way of life and an uncertain and unlooked for end” * - a continuous process Early COPD Starts in utero? In early childhood? In the workplace? At home? With first cigarette? Does an 80 year old ex-smoker with FEV1/FVC 0.65 and FEV1 80% predicted have early disease? (because it’s a bit late!) *Pinnock H et al. BMJ. 2011;342:142-52.

Does Early/Mild COPD matter? Symptoms/Quality of Life Patients underestimate/under-report severity of their disease* Physiological impairment Despite lack of symptoms, patients exhibit significant physiological impairment** Exacerbations Some patients have frequent exacerbations*** Disease progression Mild airflow obstruction may signify risk of disease progression * Rennard S et al. Eur Respir J 2002; 20: 799–805. ** O’Donnell D et al. Respirology. 2016 Feb;21(2):211-23. doi: 10.1111/resp.12619 *** O’Reily J et al. Prim Care Respir J. 2006 Dec;15(6):346-53

Screening for Early/Mild COPD Logical arguments for screening for COPD: Having abnormal lung function may encourage people to stop smoking Treatment of early disease may prevent disease progression May unmask those who actually have symptoms which they have attributed to aging Should be cost effective in long run preventing people getting worse

Screening for Early/Mild COPD Two recent evaluations of population screening for COPD (UK* and USA**) Both came to same conclusion that population screening not cost effective (in developed countries) because: No evidence that screening for COPD in asymptomatic persons improves health-related quality of life, morbidity, or mortality. No consistent evidence that detecting early COPD improves smoking cessation rates – besides everyone should stop smoking regardless of disease Both determined that early detection of COPD, before the development of symptoms, does not alter the course of the disease or improve patient outcomes However, cost-effective evidence does exist for case-finding symptomatic individuals with more advanced COPD and this should continue *Cartwright S. 2012. http://legacy.screening.nhs.uk/copd **USPTF. JAMA. 2016;315(13):1372-1377. doi:10.1001/jama.2016.2638

Effect of diagnosing COPD using spirometry on smoking quit rates Mixed results on effect of abnormal spirometry on motivating patients to quit. 5 RCTs – 1 supportive of abnormal spirometry (using lung age) improving quit rates*. One large descriptive non-randomised study supportive** Overall combined effect not thought to be significant *Parks G et al. BMJ. 2008 Mar 15;336(7644):598-600. doi: 10.1136/bmj.39503.582396.25 **Bednarek M et al. Thorax. 2006 Oct;61(10):869-73

Approach to Case Finding for Early/Mild COPD Adapted from Price D et al. Prim Care Respir J. 2009 Sep;18(3):216-23. doi: 10.4104/pcrj.2009.00055

Problems with spirometry based diagnosis of COPD What about GOLD “stage 0” (ATS/ERS – At Risk) – “normal” spirometry? Heavy smokers without symptoms – but still evidence of oxidative stress* Heavy smokers without obstruction may have significant impairment** With symptoms and evidence of significant emphysema on CT/gas transfer(up to 26%)**/*** * Rytila P. et al. Respiratory Research 2006, 7:69 doi:10.1186/1465-9921-7-69 ** Regan EA et al. JAMA internal medicine. 2015;175(9):1539-49. doi:10.1001/jamainternmed.2015.2735 *** Suranna N – Abstract PCRS meeting 2015

GOLD Stage 0 – A Lost Tribe

Approach to Case Finding for Early/Mild COPD If normal – for full lung function/HRCT Adapted from Price D et al. Prim Care Respir J. 2009 Sep;18(3):216-23. doi: 10.4104/pcrj.2009.00055

When we have found it – How should we manage Early/Mild COPD?

London Respiratory Team COPD ‘Value’ Pyramid

How should we manage Mild COPD? Apply Triple Therapy for mild COPD Avoid/minimise risk factors: Cigarette smoking, cannabis, occupational exposure, impaired childhood and adolescent lung growth, indoor and outdoor air pollution, asthma)

Effect of smoking cessation on lung function Anthonisen NR et al, JAMA 1994 272:1497

How should we manage Mild COPD? Apply Triple Therapy for mild COPD Avoid/minimise risk factors: Cigarette smoking, cannabis, occupational exposure, impaired childhood and adolescent lung growth, indoor and outdoor air pollution, asthma) Flu/pneumonia vaccination Lifestyle change: increase activity/exercise. If you don’t get breathless when you exercise – it ain’t exercise! Good nutrition

New Triple Therapy for Mild COPD Avoiding/minimising risk factors Prevents disease progression Flu vaccination Helps reduce risk of exacerbation and deteriorating lung function Exercise Reconditioning and optimising cardio-respiratory function

Patient Centred Drug treatment for Mild Symptomatic COPD Predominant Breathlessness SABA ➔ LAMA ➔LAMA+LABA ?effective in GOLD stage 0 for hyperinflation Predominant Exacerbator (trumps breathlessness) LAMA ➔LAMA+LABA or LABA+ICS ?effective in GOLD stage 0 Predominant Asthma (-COPD overlap) SABA + ICS ➔LABA+ICS

Some things to think about when you return home Is obstruction necessary in COPD? (Or should we remove the “O”?) If so, which cut-off do we use (Fixed ratio or LLN)? How will I initiate a case finding programme for at risk individuals? What will I do with symptomatic patients without obstruction – the Lost Tribe? How will I apply the new triple therapy to all my early/mild COPD patients? Is my prescribing individualised for my patient’s needs?