Respiratory Management - Tower Hamlets NMP Forum Ellen Nicholson Queens Nurse Workforce Development – NP & NMP City & Hackney GP Confederation March 2017

Declarations of Interest Received education grants for professional education from Boehringer, Speaker for Novartis, Teva Pan-London respiratory Society (PLAN) Member of PCRS/ARNS and NICE Committee Member – Asthma Management Guidelines

What this presentation covers Background Scope Key priorities Discussion NOTES FOR PRESENTERS: In this presentation we will start by providing some background to the guideline and why it is important. We will then present the key priorities for implementation. The NICE guideline contains 7 key priorities for implementation, which you can find on page 4–5 of your quick reference guide. The key priorities for implementation cover the following areas: Diagnose COPD Stop smoking Promote effective inhaled therapy Provide pulmonary rehabilitation for all who need it. Use non-invasive ventilation Manage exacerbations Ensure multidisciplinary working Next, we will summarise the costs and savings that are likely to be incurred in implementing the guideline. Then we will open the meeting up with a list of questions to help prompt a discussion on local issues for incorporating the guidance into practice. Finally, we will end the presentation with further information about the support provided by NICE. 3

Anatomy - Upper respiratory tract nose nasal cavity sinuses larynx trachea

Anatomy – Lower respiratory tract Main bronchus Bronchi Bronchioles Alveoli Trachea -The trachea is protected ventrally by c-shaped cartilage that can be palpated under the skin in the neck. Dorsally there is a band os smooth muscle that links the 2 horns of the cartilage. Longitudinal mucosal ridges are present on the posterior wall of the trachea, and correspond to thick longitudinal bundles of elastin. This elastin contributes to the elastic recoil on expiration, and the elastin fibres could link up with those in the airways including alveolar ducts and walls. Bronchi – Bronchi have interlocking spirals of smooth muscle bands, prominent submucosal mucus glands and patches of cartilage. The epithelium of the normal bronchus is pseudostratified respiratory epithelium with occasional mucus cells. Approximately 8 generations of bronchi may be present. The transition form bronchus to bronchiole takes place in the airways of about 1mm diameter. There are around 7 generations of membranous bronchioles which have a continuous layer of smooth muscle but have no submucosal glands or cartilage in their walls. 5

Mechanics of breathing Inspiration – diaphragm and external intercostals Expiration – elastic recoil (reduced by emphysema) Inspiration (inhalation) is the process of taking air into the lungs. It is the active phase of ventilation because it is the result of muscle contraction. During inspiration, the diaphragm contracts and the thoracic cavity increases in volume. This decreases the intraalveolar pressure so that air flows into the lungs. Inspiration draws air into the lungs. Expiration Expiration (exhalation) is the process of letting air out of the lungs during the breathing cycle. During expiration, the relaxation of the diaphragm and elastic recoil of tissue decreases the thoracic volume and increases the intraalveolar pressure. Expiration pushes air out of the lungs. 6

Definition of COPD Airflow obstruction that is not fully reversible Does not change markedly over several months Airflow obstruction defined: ↓ FEV1/FVC ratio (< 0.7) If FEV1 is ≥ 80% predicted Δ COPD should be made in presence of respiratory symptoms, e.g. breathlessness cough NOTES FOR PRESENTER There is no single diagnostic test for COPD. Making a diagnosis relies on clinical judgement based on a combination of history, physical examination and confirmation of the presence of airflow obstruction using spirometry. FEV1 = forced expiratory volume in 1 second FVC = forced vital capacity NICE Guideline 12 June 2010 7

Diagnosis of COPD NICE Guideline 12 June 2010

The Umbrella Disease NICE Guideline 12 June 2010

Cartilage degeneration Goblet cell hyperplasia Squamous metaplasia Airway changes in COPD Chronic bronchitis Cartilage degeneration Goblet cell hyperplasia Squamous metaplasia Smooth muscle hypertrophy Submucosal bronchial gland hypertrophy Obstructive bronchilitis Collapsed lumen Increased mucus Goblet cell metaplasia Inflammation with fibrosis Relate to signs and symptoms 10

COPD exacerbations & Effect on FEV1 Lancet, Vol. 374, Hansel TT, Barnes PJ, New drugs for exacerbations of COPD, Pages 744-55, 2009

Risk Factors COPD

Smoking 1,2 Implicated in chronic bronchitis & emphysema since 1960’s Est.15-20% of smokers develop COPD However, recent evidence: approx 50% Risk of developing COPD is dose related & affected by age smoking is started NICE: smoking pack years documented for all Smoking cessation should be offered to all COPD mortality: 86% due to smoking – UK 1. Lundbäck B et al. (2003) 2. Department of Health 2010

Smoking: Effects of Age 1 Fletcher & Peto: in 1961 - sample of men (mostly skilled manual or clerical), aged 30 - 59, working in West London; 792 pxs followed for 8yrs 1. Fletcher & Peto (1961)

Other Risk Factors Occupational dusts & chemicals Indoor air pollution Burning of open fires of wood & coal Global population at risk: Middle East, Africa, Asia Genetics: α1 antitrypsin deficiency α1 antitrypsin deficiency: a protease inhibitor that protects against lung damage It is thought that the presence of oestrogen, which stimulates the synthesis of protease inhibitors such as a-1-antitrypsin, confers protection in women

Symptoms – treatments Dyspnoea Chronic cough Sputum Other: MRC dyspnoea scale Chronic cough One of the earliest signs Often discounted by pxs as a sign of ageing Sputum Chronic bronchitis: ≥3 months in 2 consecutive yrs Change in colour or volume: COPD exacerbation? Other: Wheeze Chest tightness Fatigue Dyspnoea – persistent and progressive; worse on exertion

COPD Assessment Tool COPD Assessment Tool Measurement of the impact of COPD on persons life 8 questions Sensitive to change Simple to use for all 1www.catestonline.co.uk

MRC Dyspnoea Scale

Key priorities Diagnose COPD Stop smoking Promote effective inhaled therapy Pulmonary rehabilitation to those who need it Manage exacerbations Ensure multidisciplinary working

NICE clinical guideline 12 (2004) NICE clinical guideline 101 (2010) COPD Severity NICE clinical guideline 12 (2004) ATS/ERS 2004 GOLD 2008 NICE clinical guideline 101 (2010) Post-b/d FEV1/FVC FEV1 % predicted < 0.7 80% Mild Stage 1 (mild) Stage 1 (mild)* 50–79% Moderate Stage 2 (moderate) 30–49% Severe Stage 3 (severe) < 30% Very severe Stage 4 (very severe)** * Symptoms should be present to diagnose COPD in people with mild airflow obstruction ** Or FEV1 < 50% with respiratory failure NICE Guideline 12 June 2010

Medicines Management

Aim of Pharmacological Therapy in COPD 1 Individualised assessment of disease severity & response to treatment Appropriate pharmacological therapy can help - reduce the burden of COPD symptoms - reduce frequency of exacerbations - reduce severity of exacerbations - improve health status - improve exercise capacity 1: GOLD revised 2015

Focus: 1. RISK of exacerbation 2. Symptoms 3. Breathlessness mMRC Airflow Limitation: Low Risk High Risk 1. GOLD 2015

Algorithm for Inhaled Therapy – Where to start

Bronchodilators Alleviate airways smooth muscle tone Alleviate breathlessness by their direct affect on the airway But they also: ↓ pulmonary hyperinflation ↑ mucociliary clearance Improve respiratory muscle function Clinical benefits may be seen irrespective of any changes in lung function

Bronchodilators Relax airway smooth muscle ↓ breathlessness Onset of action is slower than in asthmatic patients 3 Classes: ß2 Agonists Anticholinergics Methylxanthines

ß2 Agonists Side Effects: Cautions: Fine tremor, esp hands Tachycardia Hypokalaemia Restlessness Hypoxaemia Cautions: Hyperthyroidism Cardiovascular disease Arryhthmias Susceptibility to QT-interval prolongation Hypertension Muscle tremor: direct effect on skeletal muscle B2 receptors Tachycardia: direct effect on atrial B2 receptors, reflex effect from increased vasodilation via B2 receptors Hypokalaemia: direct effect on skeletal muscle uptake of potassium ions via B2 receptors Hypoxaemia: increased ventilation/blood flow mismatch due to pulmonary vasodilation

Stage 1 - Inhaled short acting SABA – Short Acting Beta agonist SAMA – Short Acting Muscarinic Antagonist Examples: Salbutamol & Terbutaline (SABA) Ipratropium Bromide (SAMA)

Stage 2a – FEV > 50% LABA – Long Acting Beta agonist Example: Salmeterol & Formoterol

Long Acting ß2 Agonists – BD

Indacaterol (Onbrez Breezhaler®) Long acting ß2 agonist 1st once daily LABA Indication: maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD Licensed: all severities COPD Dose: 150mcg OD; may be increased to 300mcg OD

Bronchodilation Time to clinically significant bronchodilation: Treatment differences: ***p<0.001 vs placebo; ;†p<0.01 ††p<0.01 vs salmeterol Time to clinically significant bronchodilation: Indacaterol: 5mins Salmeterol & Tiotropium: 30mins Balint et al. Poster presented at ERS Annual Congress 2009

Olodaterol (Striverdi Respimat) Long acting ß2 agonist Once daily LABA Use in COPD only Indication: maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD Dose: 2 x 2.5mcgs Once a day

Stage 2a LAMA – Long Acting Muscarinic Antagonist Example: Tiotropium Bromide (Spiriva)

Muscarinic Antagonist Onset of action is slower than ß2 agonists Approx 30mins Bronchodilator effects longer Side effects: Dry mouth Blurred vision Paradoxical bronchospasm Glaucoma – care with nebulisers

Muscarinic Antagonist - SAMA QDS

Tiotropium Handihaler (Spiriva®) Once Daily LAMA Indication: maintenance bronchodilator in adult patients with COPD Dose: 18mcg OD How to use:

Tiotropium Respimat (Spiriva®) Once daily LAMA Indication: maintenance bronchodilator in adult patients with COPD Dose: 2.5mcg TT puffs BD How to use:

Aclidinium (Eklira®) Twice daily LAMA Indication: maintenance BD in COPD Dose: 400mcg BD (equiv to 322mcg BD) How to use:

Incruse Ellipta (Umeclidinium bromide) Once daily LAMA Indication: maintenance bronchodilator in adult patients with COPD Dosage: 55mcg 1 puff OD How to use:

Stage 2b – FEV < 50% ICS – Inhaled Corticosteroid LABA + ICS Example: Seretide 500 mcgs BD Symbicort 400/12 mcgs BD

LABA/LAMA COMBINATIONS Indicated in patients who are breathless despite being on LAMA or LABA.

Ultibro Breezhaler Once a day Glycopyrronium 43/Indacaterol 85 Dosage: T OD How to use Benefits of use: sweet taste auditory visualisation of inhaled contents

Duaklir Genuair Twice daily LAMA/LABA Aclidinium bromide 340mcg/formoterol 12mcg Dosage: 1 puff BD Benefits of use: Ideal for those with dexterity problems, can visualise inhalation, symptomatic during the night.

Anoro Ellipta Daily LABA/LAMA Umeclidinium bromide 55mcg / Vilanterol 22mcg Doseage: 1 puff OD Benefits of use Ideal for those with dexterity problems prefer once daily inhalation.

Spiolto Respimat Once daily LABA/LAMA Tiotropium 2.5mcg/Olodaterol 2.5mcg Dosage: 5mcg OD Benefits of use: Only SMI ideal for those with poor inspiratory effort.

Inhaled Corticosteroids Little/no effect on decline of lung function Guidelines: in combination with long acting ß2 agonists Mod-severe COPD FEV1 ≤50% ≥2 exacerbations/yr on optimised therapy ↓exacerbations by 25% Never used alone ↑incidence of non fatal pneumonia (TORCH study) Inflammatory airways changes do occur in COPD, however these are mediated by neutrophils – insensitive to corticosteroids. In asthma, the inflam changes are mediated by eosinophils – which respond very well to corticosteroids

ICS & LABA Combination – BD

Licensed ICS/LABA Inhalers in COPD Seretide Accuhaler 500 T BD Symbicort 200/6 TT BD Symbicort 400/12 T BD Duoresp 160/4.5 TT BD Duoresp 320/6 T BD Relvar 92/22 T OD Fostair 100/6 TT BD

ICS & LABA Combination – OD

Stage 3a – Combinations + LAMA – Long Acting Muscarinic Antagonist LABA + ICS – Long Acting Beta agonist Inhaled Corticosteroid

Stage 3b – Combinations LABA + ICS – Long Acting Beta agonist Inhaled Corticosteroid Or LABA – Long Acting Beta agonist + LAMA Long Acting Muscarinic Antagonist

Summary for Inhaled Therapy in COPD Choice of drug (s) should take into account person’s 1 - Symptomatic response - Preference to device - Ability to use the inhaler device effectively - Drugs potential to reduce exacerbations - Minimise side effects - Cost 1 NICE 2010

Medicines Management Asthma

Definition of Asthma Asthma is a chronic disease characterized by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. During an asthma attack, the lining of the bronchial tubes swells, causing the airways to narrow and reducing the flow of air into and out of the lungs. World Health Organisation NOTES FOR PRESENTER There is no single diagnostic test for Asthma. Making a diagnosis relies on clinical judgement based on a combination of history, physical examination and confirmation of the reversibility using spirometry. 57

Diagnosis of asthma Asthma is a Heterogeneous disease signifying diversity There is currently no gold standard test available to diagnose asthma Diagnosis is principally based on a thorough history taken by an experienced clinician combined with diagnostic testing

Initial assessment Wheezing Cough Breathlessness Nocturnal symptoms Diurnal and seasonal variations Personal or family history of allergies, atopic disorders or asthma Spirometry - suspect asthma if: Bronchodilator response: A significant increase in FEV1 (>12% from baseline) 1 >PEF: diurnal or day-to-day variability of ≥20%

Reference British Thoracic Society, Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma: A National Clinical Guideline. Revised Edition, 2014.

British Thoracic Society Guidelines 2016 Stepwise approach replaced by high probability, intermediate and low probability approach. This highlights short acting beta2 agonists are key ‘rescue therapy’ from symptoms or asthma attacks but should rarely be used on their own

BTS 2016

Good symptomatic response to treatment - confirm diagnosis of asthma Record how the diagnosis was made Poor response or equivocal, check inhaler technique and adherence, arrange further tests and consider alternative diagnoses. High probability of asthma: start initiation of treatment (typically 6 weeks of inhaled corticosteroids) Reasses with a validated symptom questionnaire and/or lung function tests (FEV1 or home serial peak flows

Intermediate probability of asthma Spirometry, with bronchodilator reversibility is preferred test Initiate treatment and assess the response by repeating lung function tests and objective measures of asthma control. In adults and children with an intermediate probability of asthma and normal spirometry results; Challenge tests FeNO to identify eosinophilic inflammation.

Low probability If there is a low probability of asthma and/or an alternative diagnosis is more likely, investigate for the alternative diagnosis and/or undertake or refer for further tests of asthma. BTS 2016

Pharmacological Management Aim of pharmacological therapy in asthma Global initiative for asthma (GINA) 2013, Revised 2015. 1. Individualised assessment of disease severity & response to treatment 2. Appropriate pharmacological therapy aims to: reduce the burden of asthma symptoms: 3. Reduce frequency & severity of exacerbations 4. Attainment of control correlates with a better quality of life & reduction in health care use

Approach to management Start treatment at the level most appropriate to initial severity. Achieve early control. Maintain control by: increasing treatment as necessary decreasing treatment when control is good.

Choice Choice of drug (s) should take into account person’s - Preference to device - Symptomatic response - Ability to use the inhaler device effectively - Drugs potential to reduce exacerbations - Minimise side effects - Cost Within Prescribing Framework published July 2016

Short Acting ß2 Agonists

Inhaled corticosteroids Choice of drug (s) should take into account person’s - Symptomatic response - Preference to device - Ability to use the inhaler device effectively - Drugs potential to reduce exacerbations - Minimise side effects - Cost

A high level of drug deposits within the mouth and throat Supress inflammatory/immunological responses & mitigate against airway hyper-responsiveness It takes 1-4 weeks before the benefit of Introducing/up-titrating ICS is apparent A high level of drug deposits within the mouth and throat Oral candidiasis occurs as a consequence of this. Rinsing the mouth after may reduce the risk of oral opportunistic infection Battaglia et al., 2014 Choice of drug (s) should take into account person’s - Symptomatic response - Preference to device - Ability to use the inhaler device effectively - Drugs potential to reduce exacerbations - Minimise side effects - Cost

Leukotrienes receptor agonists Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.

Leukotriene receptor agonists Leukotrienes are inflammatory mediators produced by leukocytes which contribute to bronchospasm and airway hyper-responsiveness BTS recommend as add on therapy after Combination inhaler Example drugs include: Montelukast, Zafirlukast

ICS & LABA combinations

Maintenance and Reliever Therapies (MART) Maintenance and Reliever Therapies are designed for adults (aged 18 or over). Evidence suggests MART reduces exacerbations, hospitalisation and SABA use Symbicort SMART Regime Fostair MART Regime DuoResp Spiromax MART Regime. Atienza 2009 (Atienza, Aquino et al. 2013) Papi 2013 {Papi, 2013 #405} MART (ICS low dose + LABA), Patel 2013 {Patel, 2013 #1202}

Inhaler Tree

pMDI DPI OD MART Step 1 Step 2/3 Step 3/4 Inhaler Tree – Acknowledgement to Paul Pfeffer ‘Inhaler Tree’ – Acknowledgement to Dr. Paul Pfeffer

Inhaler technique Optimal inhaled particle deposition requires a forceful inhalation for DPIs and a gentle inhalation for pMDI inhalers Lung deposition of budesonide inhaled via Turbuhaler®: a comparison with terbutaline sulphate in normal subjects. Borgstrom et al. 1994 Acknowledgement Paul Pfeffer

Multiple inhalers confuse asthma patients Study of 208 patients with a single inhaler type and 113 with multiple inhaler types. 29% error rate in patients with a single inhaler type 39% of patients with multiple inhaler types made significant errors. 32% error rate in patients with multiple DPI types. 46% error rate in patients with a pMDI and a DPI van der Palen et al. ERJ 1999

Complete asthma control defined No day time symptoms No night time awakening due to asthma No need for rescue medication No asthma attacks No exacerbations No limitations on activity including exercise Normal lung function (Fev1 and/or PEF > 80% predicted or best) Minimal medication side effects Global initiative for asthma (GINA) 2013

Muscarinic antagonist Tiotropium Respimat (Spiriva®) Onset of action is slower than ß2 agonists Approx 30mins Bronchodilator effects longer Side effects: Dry mouth Blurred vision Paradoxical bronchospasm Glaucoma – care with nebulisers Once daily LAMA Indication: maintenance bronchodilator in adult patients with asthma Dose: 2.5mcg TT puffs OD

Asthma Review Triggers Concordance and compliance – check Emis drug history Social factors Psychological factors Familial factors Smoking Self management

Personal Asthma Action Plan (PAAP)

PAAP & Asthma Review Inhaler techniques should be routinely undertaken Non-adherence should be identified and monitored Urgent review for all with more than 12 short-acting beta agonist inhalers in previous 12 months Triggers should be documented in patient notes and on asthma action plan Each review should review asthma control (asthma control test etc.) Ring et al., 2011 Gibson & Powell, 2004 Newell et al. 2015 Gibson, P; Powell, H (2004) Written action plans for asthma: an evidence-based review of the key components. Thorax. 59, 94-99 Newell, K; Lawlor, R; Bunce, R (2015) Co-creating personalised asthma action plans. Nursing Times. 111, 19: 12-15 Ring, N; Jepson, R; Hoskins, G; Wilson, C; Pinnock; H; Sheikh, A; Wyke, S (2011) Understanding what helps or hinders asthma action plan use: A systematic review and synthesis of the qualitative literature. Patient education and counseling. 85, 131-143

Assessment: Royal College of Physicians of London three questions IN THE LAST WEEK / MONTH YES NO “Have you had difficulty sleeping because of your asthma symptoms (including cough)?” “Have you had your usual asthma symptoms during the day (cough, wheeze, chest tightness or breathlessness)?” “Has your asthma interfered with your usual activities (e.g. housework, work, school, etc)?” Date / / / Outcomes and audit. Thorax 2003; 58 (Suppl I): i1-i92 Applies to all patients with asthma aged 16 and over. Only use after diagnosis has been established. © Imperial College London 86

Asthma Control Test™ (ACT) In the past 4 weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home? Score During the past 4 weeks, how often have you had shortness of breath? During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night, or earlier than usual in the morning? During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as salbutamol)? Copyright 2002, QualityMetric Incorporated. Asthma Control Test Is a Trademark of QualityMetric Incorporated How would you rate your asthma control during the past 4 weeks? Patient Total Score

Monitoring and follow up

Other Considerations

Differentiating COPD & Asthma Spirometry - suspect asthma if: Bronchodilator response: A significant increase in FEV1 (>12% from baseline) 1 >PEF: diurnal or day-to-day variability of ≥20% 11SIGN 2012

Allergic Rhinitis BSACI Guidelines The nose is the gateway to the respiratory tract and rhinitis is associated with symptoms arising from the sinuses, middle ear, the nasopharynx and lower airways. Occupational rhinitis often precedes the development of occupational asthma. Both allergic rhinitis (AR) and non-AR are risk factors for the development of asthma. Rhinitis significantly reduces quality of life interferes with both attendance and performance at school and work and results in substantial NHS costs Clinical & Experimental Allergy. Volume 38, Issue 1, January 2008, Pages: 19–42

Long acting ß2 agonists The Asthma UK report published in June 2015 ‘Patient safety failures in asthma: the scale of unsafe prescribing in the UK’ identified 22,840 people prescribed a LABA or LAMA without ICS 106,742 people prescribed more than 12 short-acting bronchodilators a year Representing   0.4% and 2%  respectively of the total 5.4 million people receiving treatment for asthma. It is dangerous to use a long-acting reliever inhaler without a steroid preventer inhaler

Summary Use inhaler device that patient is able to use Try to avoid generic prescribing Consider if diagnosis is correct if treatment is not reducing side effects or onwards referral Everyone with an asthma diagnosis should have a PAAP

Thank-you & Questions