Background information
Asthma
1
Asthma is a complex disease affecting the lungs that can be managed but cannot be cured. Asthma can be
controlled well in most people most of the time, although some people may have more persistent problems.
Asthma attacks (exacerbations) occur when symptoms worsen, and those affected can require
1
hospitalisation. There are different types of asthma; more than half of patients have Type 2 asthma, an
important distinction because the causes of inflammation that result in Type 2 asthma symptoms have been
clearly identified.
Epidemiology
There are 334 million people with asthma across the globe today, The number of asthma patients could
grow by a third within ten years due to better diagnosis and changes in diet, housing, pollution and
exposure to nature. A quarter of a million people die from asthma each year worldwide, or one person every
5,7
two minutes.
The annual costs of healthcare and lost productivity on account of asthma are €33.9 billion
in the EU. Of this, direct costs for drugs, inpatient and outpatient care were €19.5 billion, and indirect costs
€14.4 billion. A small fraction of people with asthma are estimated to have severe disease
absorb over 50% of the treatments costs
15,16
15,18
yet they
17
and account for nearly 40% of asthma deaths. It is estimated
5
that 10% of asthma patients have severe disease that is not controlled by medication. Costs for
uncontrolled patients can be more than double those for controlled patients.
14
Causes of asthma and triggers
Asthma results from inflammation of the bronchioli (which carry air in and out of the lungs), leading to
1
restricted airflow. In asthma patients, the inflamed bronchioli are more sensitive to particles in the air. When
an asthma attack occurs, mucus production is increased, muscles of the bronchioli become tight and the
lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound
associated with asthma.
2
Job code: NP/LEB/1509/0015
Date of prep: September 2015
Page 1 of 5
A number of factors can increase the chance of developing asthma, including:
4

A family history of asthma or other related allergic conditions, such as food allergy or hay fever

Having another allergic condition

Childhood bronchiolitis

Childhood exposure to tobacco smoke, particularly if exposure occurs during pregnancy

Being born prematurely, especially if ventilator support was required

Having a low birth weight as a result of restricted growth within the womb
Triggers
Triggers can be anything that irritates the lungs. When asthma patients encounter triggers, the airways
narrow and the muscles tighten around them. An increase in the production of sticky mucus (phlegm) also
occurs. Common triggers include:

4
Respiratory tract infections, particularly viral infections affecting the upper airways, such as colds
and flu

Allergens, including pollen, dust mites, animal fur or feathers

Airborne irritants, including cigarette smoke, chemical fumes and atmospheric pollution

Medicines, particularly non-steroidal anti-inflammatory drugs (NSAIDs) and beta blockers

Emotions, including stress or laughing

Foods containing sulphites, e.g. concentrated fruit juice, jam, prawns and many processed or
precooked meals

Weather conditions, including sudden changes in temperature, cold air and poor air quality

Indoor conditions, including mould or damp, house dust mites and chemicals in carpets and
flooring materials

Exercise

Food allergies, including allergies to nuts or other food items
Job code: NP/LEB/1509/0015
Date of prep: September 2015
Page 2 of 5
Symptoms and diagnosis
Asthma symptoms can range from mild to moderate or severe. The main symptoms of asthma are wheezing,
8
shortness of breath, a tight chest and coughing. Most people will only experience occasional symptoms,
but symptoms are harder to control in those with severe asthma, and they may have problems almost all the
time.
7
There are a number of ways to diagnose asthma, including lung function tests (spirometry, peak expiratory
flow test), airway responsiveness, inflammation tests, and allergy tests.
9
Severe asthma
Severe asthma can be defined as asthma that requires treatment with high dose inhaled corticosteroids
(ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’
or which remains ‘uncontrolled’ despite this therapy. Asthma control is ranked by doctors according to lung
function, symptoms and the need for reliever medication, as controlled, partly controlled and uncontrolled.
Researchers believe severe asthma is linked to a variety of factors: genetic inheritance, the age of asthma
onset, the duration of disease, exacerbations, sinus disease and inflammatory characteristics. Many patients
have difficulty breathing most of the time, as well as frequent, life-threatening attacks needing hospital
6
admissions. Severe asthma is a complex, unpredictable disease. Work and social life become limited and
every-day activities such as climbing stairs or leaving the house can be a challenge.
Most people with severe asthma are treated with a ‘one-size-fits-all’ approach, which often doesn’t control
5
their daily symptoms or improve outcomes. Patients cycle through different medicines or add on new
5
treatments to find one that relieves their symptoms, but they do not address the root cause. Not only do
many patients with severe asthma not respond to conventional treatments, many develop adverse effects
from their sustained or repeated use. These adverse events include diabetes, obesity, osteoporosis and
depression.
Type 2 asthma
9
Asthma is a heterogeneous disease. The various forms of asthma result from specific molecular pathways
in the immune system and the effects that these have on different types of inflammation in the tissues of the
lungs.
Among patients with severe asthma, the majority have Type 2. This category derives its name from
increased levels of type 2 inflammatory signals.
19
Type 2 inflammation results from the action of a specific
group of molecular messengers (cytokines) produced by the immune system, IL-13, IL-5 and IL-4. An
important mediator of Type 2 asthma is IL-13, a protein messenger released by cells that causes
inflammation. By targeting the IL-13 pathway, we have the potential to block the development of a wide
range of symptoms that are most important to severe asthma patients and that they experience nearly every
day. Blocking IL-13 activity has a broad impact on key mechanisms (such as mucus production, airway
Job code: NP/LEB/1509/0015
Date of prep: September 2015
Page 3 of 5
inflammation, narrowing and hyper-responsiveness) and the day-to-day symptoms. This could include
improvement in breathing, relief from daily symptoms, reduced limitations on daily activities, less time spent
awake at night, less use of rescue medication and reduced need for medical attention and intervention.
Treatment
Likely patient response to treatment is untested in the majority of cases, so conventional treatment is
administered in a stepwise approach, following successive treatment failure. Asthma treatment starts with
reliever therapy, followed by the addition of preventer medications, as required. In poorly controlled asthma,
other treatments may be added to the patient’s medication regimen. Treatment doses are reviewed and
altered to achieve the best control using the lowest dose.
12
Reliever medication is taken via an inhaler to relieve asthma symptoms quickly. Most often, these inhalers
contain a short-acting beta agonist (SABA) which works by relaxing the muscles surrounding the narrowed
13
airways.
Preventer inhalers work over time to reduce the amount of inflammation and sensitivity of the airways,
and reduce the chances of asthma attacks occurring. They must be used regularly (typically twice or
occasionally once daily) and indefinitely to keep asthma under control. Most often, preventer inhalers
13
contain inhaled corticosteroids.
Add-on therapies are introduced if a patient’s asthma does not respond to initial treatment. The dose of
preventer medication may be increased, or an inhaler containing a long-acting reliever (long-acting
bronchodilator/long-acting beta2-agonist, or LABA) may be prescribed.
13
Additional treatments include leukotriene receptor antagonists, theophyllines, oral steroids and injectable
monoclonal antibodies. Bronchial thermoplasty may also be used. Bronchial thermoplasty works by
destroying some of the muscles surrounding the airways in the lungs, which can reduce their ability to
narrow the airways.
13
The role of personalised treatment approaches in asthma
Identifying and targeting treatments to specific types of a disease or patient group is called Personalised
Healthcare. Already widely applied in cancer treatment, Personalised Healthcare could provide severe
asthma patients with the confidence that their medicine is right for them. The way asthma is treated will
change dramatically with several new treatments becoming available in the next decade. Treatments are
needed that target the critical underlying mechanism responsible for different types of asthma. This in turn
may eliminate the cost of trying different medicines to find one that works, and may reduce the side effects
and the burden for the patient from the use of multiple therapies to relieve symptoms.
Job code: NP/LEB/1509/0015
Date of prep: September 2015
Page 4 of 5
Presence of Type 2 messenger molecules cannot be detected with commercially-available tests, but IL-13
activity produces a protein called periostin that can be detected in the blood as a reliable biomarker for
Type 2 asthma. Periostin is the most promising biomarker for Type 2 asthma. By knowing that a patient has
Type 2 asthma, physicians could confidently prescribe a Type 2-specific treatment
References
1. NHS. Asthma. Overview. Available from: http://www.nhs.uk/conditions/asthma/Pages/Introduction.aspx#close.
Accessed: 12 November 2014
2. National Library of Medicine. National Institute of Health. Asthmatic bronchiole and normal bronchiole. Available
from: http://www.nlm.nih.gov/medlineplus/ency/imagepages/19375.htm. Accessed 12 November 2014
3. Shutterstock. Bronchoconstriction. Desigua. 161240786
4. NHS. Asthma. Causes. Available from: http://www.nhs.uk/Conditions/Asthma/Pages/Causes.aspx. Accessed 12
November 2014
5. Global Initiative for Asthma. Global burden of asthma. Available from: http://www.ginasthma.org/Global-Burden-ofAsthma. Accessed 13 November 2014
6. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med.
2008;178:218-24.
7. American Academy of Allergy Asthma & Immunology. Asthma Statistics. Available from:
http://www.aaaai.org/about-the-aaaai/newsroom/asthma-statistics.aspx). Accessed 14 November 2014
8. NHS. Asthma. Symptoms. Available at: http://www.nhs.uk/conditions/asthma/pages/symptoms.aspx. Accessed 13
November 2014
9. NHS. Asthma. Diagnosis. Available from: http://www.nhs.uk/Conditions/Asthma/Pages/Diagnosis.aspx. Accessed
November 13, 2014
10. European Lung Foundation. Severe Asthma. Understanding the professional guidelines. Available from:
http://www.europeanlung.org/assets/files/en/publications/Severe_asthma_guideline.pdf. Accessed 12 November
2014
11. European Respiratory Society. ERJ Press Releases. New guidelines for severe asthma provide an updated definition
of the disease and a new plan to tackle it. Available from:
http://erj.ersjournals.com/site/presspack/presspack13december13.html. Accessed 12 November 12, 2014
12. National Asthma Education and Prevention Program. Third Expert Panel on the Diagnosis and Management of
Asthma. National Heart, Lung, and Blood Institute (US). Available from:
http://www.ncbi.nlm.nih.gov/books/NBK7222/. Accessed 14 November 2014
13. NHS. Asthma. Treatment. Available from: http://www.nhs.uk/Conditions/Asthma/Pages/Treatment.aspx. Accessed 12
December, 2014
14. ERS White Book. The economic burden of lung disease.
http://www.erswhitebook.org/files/public/Chapters/02_economics.pdf Last accessed 31 July 2015
15. Godard P et al. Costs of asthma are correlated with severity: a 1-yr prospective study. Eur Respir J 2002; 19: 61–67
16. Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S.
17. Why asthma still kills. The National Review of Asthma Deaths (NRAD). Royal College of Physicians [England] May
2014
18. Peters SP et al. Uncontrolled asthma: A review of the prevalence, disease burden and options for treatment. Respir
Med. 2006 Jul;100(7):1139-51. Epub 2006 May 18
19. Woodruff et al. T-helper Type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care
Med. 2009 Sep 1;180(5):388-95.
Job code: NP/LEB/1509/0015
Date of prep: September 2015
Page 5 of 5