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www.woolcock.org.au
Optimising the Management of
Asthma and COPD
New strategies and treatments
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Presenter
• Dr Vicky Kritikos
• Airways Clinic Pharmacist, Asthma Centre, Royal
Price Alfred Hospital
• Clinical Lead, Respiratory Medicines Group,
Woolcock Institute of Medical Research
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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
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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
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Source: AIHW, Mortality from asthma and COPD in Australia,2014
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What is Asthma?
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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
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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
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Asthma: What’s Beneath the Surface?
Airway
inflammation
Airway
hyperresponsiveness
Symptoms
obstructionAirflow
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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
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“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
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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
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The evidence
Clinical findings indicate different patterns of disease
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Chronic obstructive lung disorders
Asthma COPDACO
ACO = asthma, COPD, overlap
Still a lot to understand
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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
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ALWAYS AVOID…
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Unavoidable triggers
RESPIRATORY TRACT
INFECTIONS
and
CERTAIN MEDICATIONS
PHYSIOLOGICAL
AND
PSYCHOLOGICAL
CHANGES
COMORBID
MEDICAL
CONDITIONS
Allergic Rhinitis
Rhinosinusitis
Reflux
Obesity
MANAGE
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DO NOT AVOID…
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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
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2
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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
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• 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
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Regardless of current treatment regimen
Can you describe good symptom control?
Australian Asthma Handbook, 2014: www.asthmahandbook.org.au
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• 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
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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
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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
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Conditions that may affect asthma symptom control
asthmahandbook.org.au
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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
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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
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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
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Asthma management is
10% medication & 90% education”1
2. 1Fink. Resp Care 2005; 50:598-600.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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• 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”
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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.
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Prevention, early detection and
treatment of exacerbations are vital
to reduce the burden of COPD
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Stepwise approach requires patients to
discontinue some previous medicines
before undertaking new treatment
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Ensure medicine classes are not duplicated
when adding or changing medicines
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COPD Therapies
• SPIRIVA Respimat
tiotropium
• SPIOLTO Respimat
tiotropium and olodaterol
• Brimica Genuair
aclidinium + eformoterol
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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
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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
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Treating exacerbations
• Bronchodilators
SABAs
anticholinergics (Atrovent)
• Oral corticosteroids
• Antibiotics
• Hospitalisation
-oxygen therapy
-ventilation
Early intervention improves recovery, QOL
and reduces hospitalisations
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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
•
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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
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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
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Questions
5