www.woolcock.org.au

Optimising the Management of

Asthma and COPD

New strategies and treatments

Presenter

• Dr Vicky Kritikos

• Airways Clinic Pharmacist, Asthma Centre, Royal

Price Alfred Hospital

• Clinical Lead, Respiratory Medicines Group,

Woolcock Institute of Medical Research

Outline

• Advances in our understanding of the most common

obstructive lung disorders

Asthma

COPD

• Discuss optimal management according to recent

guidelines and evolving directions in the treatment of

the disorders

• Questions

Burden of Asthma

• Asthma is one of the most common chronic diseases

worldwide with an estimated 300 million affected

• Prevalence is increasing in many countries,

especially in children

• Health care expenditure on asthma is very high

Poorly controlled asthma is expensive

• In Australia in 2015

Direct costs = $1.2 billion, indirect costs = $24.7 billion

Deloitte Access Economics. Asthma Australia

and National Asthma Council Australia.

November 2015: The Hidden Cost of Asthma

Source: AIHW, Mortality from asthma and COPD in Australia,2014

What is Asthma?

Asthma is a heterogeneous disease, usually

characterized by chronic airway inflammation.

It is defined by the history of respiratory symptoms

such as wheeze, shortness of breath, chest tightness

and cough that vary over time and in intensity,

together with variable expiratory airflow limitation

Definition of asthma – GINA 2016

GINA 2016

Characteristics of untreated asthma

• Chronic inflammation involving many cells

Swelling of the lining inside the airways

Increased production of mucus (plugs)

• Airway hyperresponsiveness

i.e. sensitive airways that constrict too much too easily

Constriction of airway smooth muscle

Intermittent airway narrowing airflow obstruction

Australian Asthma Handbook, 2014: www.asthmahandbook.org.au

Asthma: What’s Beneath the Surface?

Airway

inflammation

Airway

hyperresponsiveness

Symptoms

obstructionAirflow

Characteristics of untreated asthma

• Inflammation is persistent, even though

symptoms are episodic

• If untreated, structural changes in the airway wall

(airway remodelling) irreversible narrowing

permanent damage of the lungs

“Asthma is a heterogeneous disease”

• Cellular research suggests

Different inflammatory cells

> 1 complex pathway of reactions

Different clusters of mediators

• Clinical findings indicate

Different patterns of disease

The key clinical features of severity (lung function, symptoms and exacerbations),

inflammatory characteristics (particularly TH2 immunity) and their division into associated

phenotypes are shown. However, these phenotypes have not yet been fully characterized.

Asthma Phenotypes or Subgroups

Wenzel, Nat Med 18:716-725, 2012

The evidence

Clinical findings indicate different patterns of disease

Chronic obstructive lung disorders

Asthma COPDACO

ACO = asthma, COPD, overlap

Still a lot to understand

Avoidable triggers

ALLERGENS

AIRBORNE

ENVIRONMENTAL

IRRITANTS

CERTAIN

MEDICINES

AVOID OR REDUCE WHERE POSSIBLE*

*If relevant avoidance strategies are practical and shown to be effective

DIETARY

ALWAYS AVOID…

Unavoidable triggers

RESPIRATORY TRACT

INFECTIONS

and

CERTAIN MEDICATIONS

PHYSIOLOGICAL

AND

PSYCHOLOGICAL

CHANGES

COMORBID

MEDICAL

CONDITIONS

Allergic Rhinitis

Rhinosinusitis

Reflux

Obesity

MANAGE

DO NOT AVOID…

What is an asthma flare-up

• When asthma symptoms start up or get worse

compared to usual

symptoms will NOT go away by themselves and need

treatment

• Can happen quickly but can also come on gradually

over hours or days (e.g. when you catch a cold)

• Can become serious if not treated properly

A severe flare-up needs urgent treatment by a doctor

or hospital emergency department

1

2

Written Asthma Action Plans

Use of a written asthma action plan together with self

management education and regular review:

• Improves asthma control

• Reduces mortality due to asthma

• Reduce days absent from work/school.

• Reduce emergency presentations to general practice

• Reduce hospital presentations and admissions

• Improves lung function

Homepagehttp://www.asthmahandbook.org.au

• The long-term goals of asthma management are to

achieve and maintain asthma control

1. Symptom control:

to achieve good control of symptoms and

maintain normal activity levels

2. Risk reduction:

to minimise future risk of

– flare-ups

– fixed airflow limitation

– medication side-effects

Goals of asthma management

GINA 2016

Regardless of current treatment regimen

Can you describe good symptom control?

Australian Asthma Handbook, 2014: www.asthmahandbook.org.au

• Manage asthma in a continuous cycle:

Assess

Adjust treatment (step-up, step down)

Review the response

• Teach and reinforce essential skills– Inhaler skills

– Adherence

– Guided self-management education

• Written asthma action plan

• Self-monitoring

• Regular medical review

Treating to control symptoms and minimise risk

GINA 2016

Before considering stepping up, check symptoms are due to asthma, inhaler technique is correct, and adherence is adequate

Consider stepping up if good control is not achieved.

When asthma is stable and well controlled for 2–3 months, consider stepping down (e.g. reducing inhaled corticosteroid dose, or stopping long-acting beta2 agonist if inhaled corticosteroid dose is already low).

Figure. Stepped approach to adjusting asthma medication in adults

Australian Asthma Handbook v1.1 asset ID 31

Many factors contribute to poor control

• Poor adherence to regular therapy Confusion about the dose or device

Fears about the medication and its side effects

Asthma beliefs and attitudes about ill health

Underestimation of severity

Cost of medication

• Poor inhaler technique Prevents patients from gaining the maximum benefit from

their medicines

• Smoking

• Co-existing conditions

Conditions that may affect asthma symptom control

asthmahandbook.org.au

Asthma Therapy

• Relievers – SABAs

Relax smooth muscle

Do not treat inflammation

Ventolin, Asmol, Bricanyl

As needed basis

LABAS

Not to be used on their own

Add-on to ICS

NORMAL BRONCHIOLE ASTHMATIC BRONCHIOLE

Asthma Therapy

• Preventers – daily

Anti-inflammatory

Inhaled corticosteroids

Non-steroidal medication

Combination therapy (ICS/LABA)

– Breo Ellipta once a day

– SMART 100/6; 200/6mcg

NORMAL BRONCHIOLE ASTHMATIC BRONCHIOLE

Other Therapies

• Oral corticosteroids – manage flare-ups

e.g. prednisone for 5-10 days – no need to taper doses

• Antimuscarinic bronchodilators

Atrovent (ipratropium), Spiriva (tiotropium) – add-ons

• Anti-IgE therapy

Omalizumab (Xolair) – add-ons (fulfill certain criteria)

– Uncontrolled severe allergic asthma; subcutaneous injection

• Anti-IL 5 therapy

Mepolizumab (Nucala) – add-ons (fulfill certain criteria)

– severe refractory eosinophilic asthma; subcutaneous injection

Asthma management is

10% medication & 90% education”1

2. 1Fink. Resp Care 2005; 50:598-600.

Chronic Obstructive Pulmonary Disease

• Affects 1 in 20 Australian patients in general practice

• Under-recognised by doctors

• Under-reported by patients until it becomes more

advanced and begins to impair QOL

• 1 in 5 patients with COPD are classified at the

highest severity level

• May coexist or overlap with asthma

COPD

• Usually associated with long-term smoking

• Slowly progressive symptoms

breathlessness, especially on exertion, cough, sputum

• Marked by a gradual decline in lung function

• In some cases, repeated exacerbations

• Mainly affects older age group

• Poor response to inhaled therapy

• Impacts on other parts of the body

Characteristics of COPD

• Chronic inflammation mainly in

peripheral airways and tissue

Structural changes

Airway narrowing

Increased mucus production

Destruction of alveoli

Gas exchange centres

Airflow obstruction not fully reversible

COPD

• Different pattern of inflammation to that of asthma

Neutrophils produce oxidants that overwhelm the

antioxidant defense mechanism oxidative stress

• Oxidative stress is a critical feature

• Effect of cigarette smoke (other irritants)

1. Promote inflammation and oxidant production

2. Impair the innate defense mechanisms

COPD: A Systemic Disease

Inflammatory

mediators in

the

circulation

Skeletal

Muscle

Weakness

Cachexia

Metabolic

Diseases

Bone

Disease

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. January 2015.

Inflammation

in the lungAirflow limitation

Hyperinflation

Pneumonia

Lung

cancer

‘Spill-over’

Cardiovascular

Diseases

Comorbidities• Pneumonia

• Cardiovascular diseases

• Skeletal muscle dysfunction

• Osteoporosis

• Diabetes and metabolic syndrome

• Anxiety and depression

• Obesity or malnutrition + weight loss

• Sleep apnoea and lung cancer

• Pulmonary hypotension

Hypoxia, polycythaemia, fatigue

GORD (increased risk of exacerbations)

COPDOutcomes

www.lungfoundation.com.au

COPD-X Concise Guide for Primary Care

• C – case finding and confirm diagnosis

• O – optimise lung function

• P – prevent deterioration

• D – develop support network

+ self-management plans

• X – manage exacerbations

Launched November 2014

COPD Treatment

Based on assessment of COPD Severity

Lung function (post-bronchodilator FEV1 % predicted)

COPD-X: 1 of 3 categories of severity

Level of breathlessness

Impact of symptoms on daily activities

History of exacerbations

Complications and/or comorbidities

No medication to date has been shown

to alter the decline in lung function

COPD

Severity

FEV1 (%

predicted)

Symptoms History of

exacerbations

Comorbid

conditions

MILD 60-80 Breathlessness on moderate exertion

Recurrent chest infections

Little or no effect on daily activities

Frequency may

increase as

severity

worsens

Present

across all

severity

groups

MODERATE 40-59 Increasing dyspnoea

Breathlessness walking on level ground

Increasing limitation of daily activities

Cough and sputum production

Exacerbations requiring OC and/or AB

SEVERE < 40 Dyspnoea on minimal exertion

Daily activities severely curtailed

Experiencing regular sputum

production

Chronic cough

COPD – X Guidelines

Guide to the severity of COPD

www.lungfoundation.com.au

• Reduce symptoms

Relieve symptoms

Improve exercise tolerance

Improve health status

• Reduce risk

Prevent and treat exacerbations

Reduce mortality

Prevent disease progression

Goals of pharmacological treatment

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis,

management, and prevention of chronic obstructive pulmonary disease. January 2015.

“… treat the patient today”

“… prevent them tomorrow”

Acute event, precipitated by

lower respiratory tract infections (bacteria or viruses)

exposure to pollutants or unknown factors

Characterised by a change beyond normal day-to-day

variations in the patient’s baseline: dyspnoea, cough, sputum

May warrant a change in medication or hospitalisation

Exacerbations tend to cluster an can occur across all

severity groups

What is an exacerbation?

Abramson M et al. COPD-X Concise Guide for Primary Care. Brisbane. Lung Foundation Australia. 2014.

Prevention, early detection and

treatment of exacerbations are vital

to reduce the burden of COPD

Stepwise approach requires patients to

discontinue some previous medicines

before undertaking new treatment

Ensure medicine classes are not duplicated

when adding or changing medicines

COPD Therapies

• SPIRIVA Respimat

tiotropium

• SPIOLTO Respimat

tiotropium and olodaterol

• Brimica Genuair

aclidinium + eformoterol

ICS are known to increase the risk of developing

pneumonia in patients with COPD

Does this risk vary for different agents?

i.e. are there intra-class differences between agents?

Yes, fluticasone more likely to be associated with pneumonia

ICS and pneumonia

Suissa S et al. Thorax 2013; 68:1029–36.

1. Calverley PM, et al. N Engl J Med. 2007;356:775-89;

2. Crim C, et al. Eur Respir J. 2009;34:641-7.

TORCH = Towards a Revolution in COPD Health trial

COPD Therapy

• Bronchodilators: short-acting: SABA, SAMA

• Bronchodilators: long-acting: LABA, LAMA (Spiriva)

• Inhaled corticosteroids

• Combination therapy (ICS/LABA)

• Short-term oral corticosteroids

• Antibiotics for infections

• Theophylline

• Mucolytic therapies (bromhexine, acetyl-cysteine)

Vaccination

Treating exacerbations

• Bronchodilators

SABAs

anticholinergics (Atrovent)

• Oral corticosteroids

• Antibiotics

• Hospitalisation

-oxygen therapy

-ventilation

Early intervention improves recovery, QOL

and reduces hospitalisations

Other therapies for COPD

• Smoking cessation

Nicotine replacement therapies

Bupropion

Varenicline

• Home oxygen therapy

advent of the portable oxygen concentrator

• Breathing exercises

• Inspiratory muscle training

• Physiotherapy PEP devices, Acapella or Flutter devices

•

Pulmonary rehabilitation

• should be provided to all patients with COPD

reduces dyspnoea and fatigue

reduces anxiety and depression

improves exercise tolerance

Improves QOL and emotional function

reduces hospitalisation and

shown to be cost-effective

Annual influenza & pneumococcal vaccines

Non-pharmacological strategies

Current Recommendations

• While there are many new treatments under development for the treatment lung diseases there is not enough evidence to support their general use at this stage

• Increasing evidence suggests that our current strategies are having a noticeable impact on the disease processes of both Asthma and COPD

Adherence

Inhaler technique

Regular review

We await future research with interest and optimism

Questions

5