Best care management in COPD and asthma Diagnosis and treatment in Asthma COPD overlap Professor Hilary Pinnock Asthma UK Centre for Applied Research, The University of Edinburgh General Practitioner Whitstable Medical Practice, Kent November 2018

Declaration of interests Teva Declaration of interests Airsonett, ALK-Abello, Allergy Therapeutics, AstraZeneca Bausch and LoMe, Boerhinger Ingelheim Chiesi, Cipla GSK, Johnson and Johnson, Mead Johnson Nutrition, Meda, Mylan Napp Pharmaceuticals, Novartis ThermoFisher, Napp, Nutrica. Pfizer Teva Vitalograph

Asthma Airway inflammation Eosinophilic infiltration Mast cells activation Asthma GINA guidelines: http://ginasthma.com Reversible airway narrowing Bronchoconstriction Mucosal oedema Excess mucus secretion Hyperresponsiveness +/- Airway remodelling Thickened basement membrane Muscle hypertrophy Increased goblet cells

COPD Cigarette smoking or other irritant Recurrent infections GOLD guidelines: http://goldcopd.org Recurrent infections Mucus hypersecretion Gas Exchange Abnormalities Small airway inflammation Neutrophils and macrophages Repair and airway fibrosis Airway collapse Loss of alveolar structure Decrease elastic recoil Air trapping

Reversible Airflow limitation Irreversible It ought to be easy to distinguish asthma from COPD… Asthma COPD Mast cells Eosinophils Triggers Smoking Macrophages Neutrophils Reversible Hyper-responsiveness Bronchoconstriction Alveolar destruction Small airway fibrosis Airflow limitation Irreversible

Asthma highly probable Suspected asthma: Watchful waiting (if asymptomatic) or Commence treatment, Assess response objectively Adjust maintenance dose Provide self-management Arrange on-going review Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness Structured clinical assessment (from history and examination of previous medical records) Look for: Recurrent episodes of symptoms; Recorded observation of wheeze; Symptom variability; Personal history of atopy; Absence of symptoms of alternative diagnosis Record of peak flow variability or obstructive spirometry/reversibility Code as: Suspected asthma Asthma highly probable Commence treatment (lung function/validated symptom score) Good response Asthma Low probability of asthma Investigate/treat for other more likely diagnosis Other diagnosis confirmed Intermediate probability of asthma Test for airway obstruction Spirometry Poor response Test for variability: Reversibility PEF charting Challenge tests Test for eosinophilic inflammation or atopy: FeNO Blood eosinophils, SPT, IgE Other diagnosis unlikely Options for investigations are:

Three of my patients Low Intermediate High Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness Three of my patients Low Intermediate High

Structured clinical assessment ✓ Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness Recurrent episodes (attacks) of symptoms Recorded observation of wheeze heard by a professional Symptoms of wheeze, cough, breathlessness and dyspnoea that vary over time Personal/family history of other atopic conditions No symptoms/signs to suggest alternative diagnoses. Low Intermediate High

Structured clinical assessment ✓ Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness Wheezing after URTI and in pollen season Asymptomatic between episodes Recent acute attack. PF 250l/min Wheeze heard by GP PF after steroids. 500 l/min Chest clear Non-smoker Low Intermediate High

Q Structured clinical assessment ✓ Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Wheezing after URTI and in pollen season Asymptomatic between episodes Recent acute attack. PF 250l/min Wheeze heard by GP PF after steroids. 500 l/min Chest clear Non-smoker Q Asthma is highly probable: I am happy to start treatment Asthma is highly probable, but I want to confirm with spirometry She has probably got COPD It might be asthma and COPD, I need some investigations Low Intermediate High

Structured clinical assessment Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Wheezing after URTI and in pollen season Asymptomatic between episodes Recent acute attack. PF 250l/min Wheeze heard by GP PF after steroids. 500 l/min Chest clear Non-smoker Spirometry is likely to be normal… Low Intermediate High

Asthma highly probable Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Adjust maintenance dose Provide self-management Arrange on-going review Code as: Suspected asthma Asthma highly probable Commence treatment Assess response objectively (lung function/validated symptom score) Good response Asthma Initiating treatment Code as ‘suspected asthma’ Initiate treatment (typically ICS) Assess response (validated questionnaire, FEV1,serial PFs) ✓ No response, discontinue medication, reconsider Good response, code ‘asthma’, record basis of diagnosis Provide self-management education (PAAP) before arranging repeat prescribing Adjust treatment Low Intermediate High

Q Structured clinical assessment ✓ Smoker Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Smoker Insidious development of dyspnoea over last 20 years Productive cough Inexorable deterioration Little variability Q Asthma is highly probable: I am happy to start asthma treatment COPD is highly probable, but I want to confirm with spirometry It might be asthma and COPD, I need some investigations I don’t know what the problem is… Low Intermediate High

Structured clinical assessment Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Smoker Insidious development of dyspnoea over last 20 years Productive cough Inexorable deterioration Little variability FEV1 = 28% predicted: FEV1/FVC = 51% Bronchodilator reversibility 18% (210mls) Low Intermediate High

Low probability of asthma Presentation with respiratory symptoms: wheeze, cough, dyspnoea, chest tightness ✓ Structured clinical assessment Low probability of asthma Investigate/treat for other more likely diagnosis Other diagnosis confirmed Low Intermediate High

? Brian: 61yr old garage owner Wheezy after an URTI Smoker Tendency to chestiness as a child Has been given blue inhalers in the past Pre-bronchodilator peak flow: 200 Post-bronchodilator peak flow: 240 ?

? Brian: 61yr old garage owner Wheezy after an URTI Smoker Tendency to chestiness as a child Has been given blue inhalers in the past ? Pre-bronchodilator peak flow: 200 Post-bronchodilator peak flow: 240

? Brian: 61yr old garage owner FEV1 = 66% predicted: FEV1% = 62% ? Wheezy after an URTI Smoker Tendency to chestiness as a child Has been given blue inhalers in the past FEV1 = 66% predicted: FEV1% = 62% Bronchodilator reversibility 10% (190mls) ? ? Restrictive

Asthma-COPD overlap A help or a hindrance? Diagnosis Management Multimorbidity A help or a hindrance?

A help or a hindrance?

Terminology and definitions are (part of) the problem A help if: It focuses attention on the additional complexity of co-morbidity A hindrance if: It creates another condition (‘syndrome’) It confuses patients and professionals Terminology and definitions are (part of) the problem

Terminology and definitions are (part of) the problem COPD is a slowly progressive disorder characterised by airflow obstruction that does not change markedly over several months. [BTS 1997] Asthma COPD Bronchitis Emphysema Terminology and definitions are (part of) the problem

COPD is… characterised by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. [GOLD 2018] Asthma is a heterogeneous disease, usually characterised by chronic (eosinophilic) airway inflammation. It is defined by a history of respiratory symptoms … that vary over time and in intensity together with variable airflow limitation. [GINA 2018] Different definitions Different pathophysiology Different cause/risk factors Different demography Different epidemiology Different clinical course Different response to treatment Asthma COPD Asthma COPD Bronchitis Emphysema

COPD is… characterised by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. [GOLD 2015] Different definitions Different pathophysiology Different cause/risk factors Different demography Different epidemiology Different clinical course Different response to treatment Asthma COPD Bronchitis COPD Asthma Emphysema Asthma is a heterogeneous disease, usually characterised by chronic (eosinophilic) airway inflammation. It is defined by a history of respiratory symptoms … that vary over time and in intensity together with variable airflow limitation. [GINA 2015]

COPD and asthma Some patients with COPD have some reversibility Some patients with asthma have a progressive course Barnes et al. Am J Respir Crit Care Med 2006;174:240–244 This might be evidence of a continuum from asthma to COPD and these atypical patients falling somewhere in between. However, it is more likely that both of these very common diseases may occur concurrently in some patients.

Two common diseases…. … will occur concurrently in some patients

ACOS Asthma-COPD overlap ‘syndrome’... ACOS is characterised by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD.

ACOS Asthma-COPD overlap ‘syndrome’... There is a phenotype of COPD that is difficult to separate from asthma: eosinophilia in sputum, positive bronchodilator test history prior to the age of 40, including allergic rhinitis high total IgE personal history of atopy J.J. Soler-Catalun a et al. Arch Bronconeumol. 2012;48:331–337 ACOS

ACOS Asthma-COPD overlap ‘syndrome’... There is a phenotype of asthma that is: Non-eosinophilic Tendency to be obese More likely to be female Less atopic High symptom scores Haldar et al. Am J Respir Crit Care Med 2008; 178:218-224 Moore et al. Am J Respir Crit Care Med 2010; 181:315-323 ACOS ACOS?

Asthma-COPD co-morbidity Barnes et al. Am J Respir Crit Care Med 2006;174:240–244 However, it is more likely that both of these very common diseases may occur concurrently in some patients.

Asthma-COPD co-morbidity Nissen et al. Br J Gen Pract 2018;68:e775-e782 351 patients with asthma 52 (14.8%) also had COPD 400 patients with COPD 58 (14.6%) also had asthma

Diagnosis

Does the patient have chronic airflow limitation? Take a good history… Symptoms of cough, sputum, wheeze, breathlessness Age of onset Risk factors Variability

Balance the probabilities

Balance the probabilities 3+ =

3+ = 3+ Spirometry Substantial variability Obstructive spirometry = Reversibility but not to normal 3+

Managing asthma + COPD?

Management Inhaled steroids No monotherapy with LABA Advise smoking cessation Management Inhaled steroids No monotherapy with LABA Start with treatment for asthma Support self-management Promote exercise Pulmonary rehabilitation Bronchodilators No monotherapy with ICS

Referral Refer for expert advice and evaluation Diagnostic uncertainty Failure to respond to treatment Complex co-morbidities ‘Red flags’

Multimorbidity

Asthma-COPD co-morbidity 3,885 adults in Spain Screened for COPD 385 (10.1%) were diagnosed with COPD, 67 (17.4%) had a previous diagnosis of asthma Patients with COPD and asthma had: More dyspneoa and wheezing More co-morbidities More frequent exacerbations Worse quality of life despite similar age & lung function, and less likely to be smokers Miravitles et al. Respir Med 2013; 107: 1053-60

It focuses attention on the additional complexity of co-morbidity Hospital episodes Anderson et al. Clin Respir J 2013; 7: 342–346 105,122 adults in Finland It focuses attention on the additional complexity of co-morbidity

Multimorbidity in COPD 50yrs 65yrs 1 condition 2 conditions 3 conditions 4 conditions 5 conditions 6 conditions 7 conditions 8 conditions “Multimorbidity is becoming the norm rather than the exception…” Barnett et al. Lancet 2012; 380: 37–43

Multimorbidity in COPD ? Barnett et al. Lancet 2012; 380: 37–43

Take home messages 10-20% of people with COPD also have asthma Despite descriptions of the overlap as a ‘syndrome’ this is likely to be co-morbidity in most cases. The co-morbidity is important because of the increased morbidity Diagnosis depends on a good history, looking for features of both asthma and COPD Manage the asthma first Remember the impact of multimorbidity Take home messages

Best care management in COPD and asthma Diagnosis and treatment in Asthma COPD overlap Professor Hilary Pinnock Asthma UK Centre for Applied Research, The University of Edinburgh General Practitioner Whitstable Medical Practice, Kent