Module 1 - GSKpro · 2018. 3. 21. · Accordini S, Corsico AG, Braggion M et al. Int Arch Allergy Immunol 2013;160(1):93-101; 6. Antonicelli L, Bucca C, Neri M et al. Eur Respir J

Recognising the impact of asthma

Module 1

Date

of

pre

para

tion

: A

pril 2016.

Zin

c c

ode:

NO

CL/N

LA

/0007/1

6.

1

2

3

4

5

6

Learning objectives


Living with asthma

Asthma cost and community burden

Severe asthma morbidity and mortality

Asthma pathology and development

7 How severe asthma differs from milder forms

8 Summary

Date of preparation: April 2016. Zinc code: NOCL/NLA/0007/16.

Learning objectives

• Appreciate how asthma affects work and personal life

• Learn about the financial impact of asthma on a community

• Appreciate how asthma develops in the body

• Explain how severe asthma is different from milder forms of asthma

• Recognise asthma risk factors

• Understand asthma exacerbations and their causes

• Realise the morbidity and mortality of severe asthma





QoL, quality of life.

1. Cottini M, Asero R. Eur Ann Allergy Clin Immunol 2013;45(1):17-24; 2. Hyland ME, Whalley B, Jones RC, Masoli M. Qual Life Res 2015;24(3):631-9.

Asthma is a complex, heterogeneous disease and its symptoms and severity vary

greatly among individuals1,2

Continuous learning about asthma is

important for providing the best available

treatment for patients

Knowing and understanding the true

impact asthma can have on patients’ QoL,

the community and the healthcare system

is an essential part of optimising

treatment and improving outcomes


The problem of asthma and severe asthma

1. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries,

1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386(9995):743-800; 2. Chanez P, Wenzel SE, Anderson GP et al. J Allergy Clin Immunol 2007;119(6):1337-48; 3.

Moore WC, Bleecker ER, Curran-Everett D et al. J Allergy Clin Immunol 2007;119(2):405-13; 4. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73; 5. Hekking PP, Wener RR, Amelink M et al.

J Allergy Clin Immunol 2015;135(4):896-902; 6. World Health Organization (2007). Available at: http://www.who.int/gard/publications/GARD%20Book%202007.pdf. Last accessed November 2015; 7. To T, Daly C,

Feldman R, McLimont S. BMC Public Health 2012;12:293 doi: 10.1186/1471-2458-12-293..

~242 million people affected

by asthma worldwide1

5-10% of them have

severe asthma2-5

250,000 deaths annually caused by asthma6,7


What is severe asthma?

1. Asthma UK. Available at: http://www.asthma.org.uk/advice-severe-asthma. Last accessed November 2015.

Someone with severe asthma:1

Feels short of

breath doing daily

activities

Often has serious

asthma exacerbations

Requires specialist

care and support

Needs multiple

high-dose medications


Living with asthma


Living with asthma

1. GINA. The Global Asthma Report, 2014. Available at: http://www.globalasthmareport.org/resources/Global_Asthma_Report_2014.pdf. Last accessed November 2015; 2. Hyland ME, Whalley B, Jones RC, Masoli

M. Qual Life Res 2015;24(3):631-9; 3. Siroux V, Boudier A, Anto JM et al. Allergy 2008;63(5):547-54.

The clinical characteristics of asthma can differ from person to person and will

depend on factors such as age, comorbidity pattern, triggers and severity level1

Inability to participate in certain activities

or physical exercise due to trigger

exposure2,3

Severe asthma has a greater impact on patients’ lives than milder forms.1

Examples of these limitations include:

Difficulty keeping a job due to impaired

ability to work2



1. Luskin AT, Chipps BE, Rasouliyan L et al. J Allergy Clin Immunol Pract 2014;2(5):544-52.e1-2. doi: 10.1016/j.jaip.2014.02.011; 2. Aburuz S, Gamble J, Heaney LG. Respirology 2007;12(2):227-33; 3. Lloyd A,

Price D, Brown R. Prim Care Respir J 2007;16(1):22-7; 4.Lorig KR, Ritter P, Stewart AL et al Med Care 2001;39(11);1217-23; 5. Amelink M, Hashimoto S, Spinhoven P et al. Respir Med 2014;108(3):438-44.

A limited quality of life

Severe asthma

patients with frequent

exacerbations have a

significantly reduced

health-related QoL

due to:1-3

A greater severity and number of asthma

exacerbations1

Increased time spent in hospital for outpatient

appointments, emergency department visits

and/or admissions4

The significant impact on their mental

well-being5


Severe asthma patients can be greatly affected by their

condition1,2

1. Luskin AT, Chipps BE, Rasouliyan L et al. J Allergy Clin Immunol Pract 2014;2(5):544-52.e1-2. doi: 10.1016/j.jaip.2014.02.011; 2. Chen H, Blanc PD, Hayden ML et al. Value Health 2008;11(2):231-9.

Severe asthma patients are twice as likely to experience impairments in everyday

life versus patients with mild or moderate disease.2

(N=2529)

0

10

20

30

40

50

0

10

20

30

40

50

32%

18%

0

10

20

30

40

50

41%

21%

Impairment at work Impairment at school Impairment in daily activities

Severe Mild/

moderate

Severe Mild/

moderate

Severe Mild/

moderate

p<0.0001 p<0.0001 p<0.0002

28%

14%

Imp

airm

ent (%

)

Imp

airm

ent (%

)

Imp

airm

ent (%

)


Severe asthma

presents possible

financial burdens

when it limits a

patient’s ability to

work2

Patients may find

it difficult to keep

a job if asthma

limits their ability

to work1

As asthma control

decreases, ability

to work becomes

increasingly

impaired2

Impact on working life

1. Hyland ME, Whalley B, Jones RC, Masoli M. Qual Life Res 2015;24(3):631-9; 2. Chen H, Blanc PD, Hayden ML et al. Value Health 2008;11(2):231-9.


Potential effects of a high-dose steroid-based medication

regimen

ICS, inhaled corticosteroids; OCS, oral corticosteroids.

1. Hyland ME, Whalley B, Jones RC, Masoli M. Qual Life Res 2015;24(3):631-9; 2. Walsh LJ, Wong CA, Oborne J et al. Thorax 2001;56(4):279-84; 3. Walsh LJ, Lewis SA, Wong CA et al. Am J Respir Crit Care Med

2002;166(5):691-5; 4. Kim SY, Yoo CG, Lee CT et al. J Korean Med Sci 2011;26(2):264-7.

Mood (depression,

irritability and anxiety)1

Broken bones due

to osteoporosis2,3

Obesity1

Cataracts1,2

Steroid-induced

diabetes4

OCS as add-on therapy to high-dose ICS plus controllers may be associated

with side effects that impact on patients in terms of:




1. Omachi TA, Iribarren C, Sarkar U et al. Ann Allergy Asthma Immunol 2008;101(2):130-6; 2. Walsh LJ, Wong CA, Oborne J et al. Thorax 2001;56(4):279-84; 3. Walsh LJ, Lewis SA, Wong CA et al. Am J Respir Crit

Care Med 2002;166(5):691-5.


Patients with severe asthma are

at increased risk of morbidity and

mortality compared with the

general population1

This is linked to both the disease

and the medications used to treat

the disease1-3


1. Omachi TA, Iribarren C, Sarkar U et al. Ann Allergy Asthma Immunol 2008;101(2):130-6; 2. Alvarez G, Schulzer M, Jung D, Fitzgerald JM. Can Respir J 2005;12(5):265-70; 3. Royal College of Physicians.

Available at: http://www.rcplondon.ac.uk/projects/national-review-asthma-deaths. Last accessed November 2015.

Asthma-related deaths

The likelihood of death related to severe

asthma increases with disease severity1

One of the strongest predictors of

asthma-related death is asthma-related

hospitalisation, which includes

hospitalisation as a result of an

exacerbation2

Asthma deaths in the UK have fluctuated over the years

but have not significantly decreased since 2007

Showing combined data for males and females ≥20 years in the UK between 1979 and

2011. From Royal College of Physicians, 2014.3


Asthma cost and community burden


Cost of asthma treatment

Figure is not to scale and is for illustrative purposes only.

1. Serra-Batlles J, Plaza V, Morejón E, Comella A, Brugués J. Eur Respir J 1998;12(6):1322-6; 2. Accordini S, Bugiani M, Arossa W et al. Int Arch Allergy Immunol 2006;141(2):189-98; 3. Kupczyk M, ten Brinke A,

Sterk PJ et al. Clin Exp Allergy 2014;44(2):212-21; 4. Godard P, Chanez P, Siraudin L et al. Eur Respir J 2002;19(1):61-7; 5. Accordini S, Corsico AG, Braggion M et al. Int Arch Allergy Immunol 2013;160(1):93-101;

6. Antonicelli L, Bucca C, Neri M et al. Eur Respir J 2004;23(5):723-9.

Compared with mild or moderate asthma patients, severe asthma patients have:

Costs rise with disease severity1,4-6

Total severe asthma costs are estimated to be 5x greater than for mild asthma1

Higher medication

usage1,2

Higher costs related to

physician visits1,2

Higher costs related to exacerbations,

which are also more frequent3

Higher costs related to hospitalisation

or emergency department visits1,2


GINA, Global Initiative for Asthma.

1. Antonicelli L, Bucca C, Neri M et al. Eur Respir J 2004;23(5):723-9.

Severe asthma costs are considerably higher than

mild or moderate disease

Direct and indirect costs of asthma correlate with severity1

Adapted from Antonicelli, et al. 2004.1


The socioeconomic burden of asthma exacerbations

1. Cisternas MG, Blanc PD, Yen IH et al. J Allergy Clin Immunol 2003;111(6):1212-8; 2. De Carvalho-Pinto RM, Cukier A, Angelini L et al. Respir Med 2012;106(1):47-56; 3. ENFUMOSA Study Group. Eur Respir J

2003;22(3):470-7.

Asthma exacerbations (especially those requiring hospitalisation)

are associated with high treatment costs1-3

In a US study,

hospitalisations were

responsible for 17%

($2122) of the direct

medical costs per patient

with severe asthma1

In a sample of severe

asthma patients in Brazil,

34% (n=25) had been

hospitalised in the previous

year2

In a cross-sectional

European study, 39.5%

(n=64) of those with

severe asthma had been

hospitalised at least once

in the past year3

34% 39.5%

17%

4%


As asthma control decreases, economic costs increase1

Graph based on the ATAQ index score (based on severity of asthma versus cost for medication, emergency department visits, hospital nights, physician visits and

work/school days lost). ATAQ is a validated self-administered questionnaire that assesses the patient's perceived control of their asthma. ATAQ score rates

asthma-related barriers on a scale of 0-4, with 0 representing no asthma control problems. Adapted from Sullivan, et al. 2007.1

0

Economic costs of asthma after 24 months follow-up in 3916 US patients1

ATAQ, Asthma Therapy Assessment Questionnaire.

1. Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE; TENOR Study Group. Allergy 2007;62(2):126-33.


Asthma pathology and development


What is asthma?

1. Wenzel SE. Nat Med 2012;18(5):716-25; 2. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812;

3. Walford HH, Doherty TA. J Asthma Allergy 2014 11;7:53-65. doi: 10.2147/JAA.S39119. eCollection 2014..

Healthy airway

Mucous lining

Healthy smooth muscle

Blood vessels

Open lumen

Asthmatic airway

Excess mucus

Contracted smooth muscle

with inflammation and

swelling

Reduced lumen

diameter

Blood vessels with

immune cell infiltration

Asthma is a complex, heterogeneous clinical syndrome1-3 characterised by variable airflow

obstruction, airway hyperresponsiveness and cellular inflammation2

Adapted from Holgate and Sly, 2014.2


Asthma is a developmental disease

Th2, T-helper cell type 2.

1. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812; 2. Barnes PJ. Chapter 254: Asthma. In:

Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015

• Asthma develops from complex interactions between a variety of environmental exposures

and a number of underlying genetic predispositions1

• Many features of asthma are thought to occur following environmental exposure during

foetal development or shortly after birth1

• The consequences of the exposures vary depending on the developmental stage of the

respiratory and immune systems, and underlying genetic factors1

• A number of cellular components are involved in asthma development - many of which

overlap1,2

- Allergen exposure is followed by crosstalk with the adaptive immune system, which results in a Th2

cytokine response, smooth muscle contraction and tissue remodelling1,2



1. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73; 2. GINA. The Global Asthma Report, 2014. Available at: http://www.ginasthma.org/documents. Last accessed November 2015; 3. Holgate

ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812.

Asthma symptoms

Symptoms include

dyspnoea, wheezing,

coughing, chest tightness

and nocturnal awakenings,

which can be persistent1,2

The underlying

pathophysiology causing

these symptoms is:

variable airflow

obstruction, airway

hyperresponsiveness and

cellular inflammation3

Long-term asthma

manifestations include

exacerbations, loss of lung

function, impairment of

QoL and comorbidities2


1. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812; 2. Barnes PJ. Chapter 254: Asthma. In:

Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015.

The pathophysiology of asthma

Inflammation in asthma is generally

characterised by the presence of

eosinophils and related mediators1

These are responsible for the airway

inflammation, injury and tissue

remodelling processes that are

critical components in asthma

pathogenesis1

People with asthma harbour a

particular type of inflammation in the

airways that makes them more

responsive than people without

asthma to a wide range of triggers2

The inflammation is associated with

airway hyperresponsiveness2


IgE, immunoglobulin-E; IL-25, interleukin-25; Th2, helper T-cell; TSLP, thymic stromal lymphopoietin.

1. Holtzman MJ, Byers DE, Alexander-Brett J, Wang X. Nat Rev Immunol 2014;14(10):686-98; 2. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders

Elsevier, PA, USA: 2014; 3. Barnes PJ. Chapter 254: Asthma. In: Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015; 4. Kindt TJ, et al.

Kuby Immunology. 6th ed. W.H. Freeman and Company, Basingstoke, UK: 2012; 5. Naik SR, Wala SM. Recent Pat Inflamm Allergy Drug Discov 2013;7(1):62-95; 6. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J

2014;43(2):343-73; 7. Calamita Z, Potthast SB. Inflamm Allergy Drug Targets 2013;12(1):12-18; 8. Vijverberg SJ, Hilvering B, Raaijmakers JA et al. Biologics 2013;7:199-210. doi: 10.2147/BTT.S29976.; 9. Davoine F, Lacy P. Front

Immunol 2014; 5:570. doi: 10.3389/fimmu.2014.00570; 10. Brusselle GG, Maes T, Bracke KR. Nat Med 2013;19(8):977-9.

Immune interactions in asthmatic airway inflammation (Click on the highlighted areas to learn more)

Inhaled allergens such as pollen

come into contact with the airway

epithelial cells and activate

inflammatory processes.1

Mast cells are activated in asthma

patients’ airway epithelia and smooth

muscle.2,3

IgE on mast cell membranes can

directly bind allergens, resulting in

mast cell degranulation and release of

inflammatory mediators such as

histamine.3-5

Basophils, like mast cells, are key

participants in allergic disease. They

release inflammatory and

bronchoconstriction mediators when

activated via membrane-bound IgE

binding to allergens.5

Dendritic cells are antigen-presenting

cells in the airway epithelium and the

circulation. They activate and recruit

Th2 cells by processing and

presenting allergens, and responding

to cytokines such as IL-25 and TSLP.3 T cells respond to specific allergens.

They are important in asthmatic

airway inflammation, where they

release Th2 cytokines in proportion to

disease severity.2,3,6

B cells play a role in chronic allergic

disease via antigen presentation and

produce specific Ig such as IgE.2,4

Receptor-bound IgE molecules trigger

mast cell degranulation, resulting in

vasodilation, mucus secretion and

bronchoconstriction.7,8

Eosinophils contribute to both allergic

and non-allergic inflammatory

responses.9,10

Eosinophil inflammatory processes are

linked to airway hyperresponsiveness

development and airway epithelial

damage.5


IgE, immunoglobulin E; IL-5/13/25/33; interleukin-5/13/25/33; ILC2, innate lymphoid cell type 2; Th2, T-helper cell type 2; TSLP, thymic stromal lymphopoietin.

1. Holtzman MJ, Byers DE, Alexander-Brett J, Wang X. Nat Rev Immunol 2014;14(10):686-98; 2. Kindt TJ, et al. Kuby Immunology. 6th ed. W.H. Freeman and Company, Basingstoke, UK: 2012; 3. Chang YJ,

DeKruyff RH, Umetsu DT. J Leukoc Biol 2013;94(5):933-40; 4. Barnes PJ. Chapter 254: Asthma. In: Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/.

Last accessed November 2015; 5. Scanlon ST, McKenzie, ANJ. Curr Opin Immunol 2012;24(6):707-12; 6. Brusselle GG, Maes T, Bracke KR. Nat Med 2013;19(8):977-9.


Exogenous allergens and irritants

such as pollution, microorganisms and

pollen come into contact with the

airway epithelial cells and activate

inflammatory processes.1

Airway epithelial cells defend

against microorganisms, gases and

allergens. They respond to exogenous

and endogenous triggers via pattern

recognition receptors and release

inflammatory mediators such as IL-25

and TSLP, which attract and activate

other immune cells.1

Macrophages are involved in both

innate and adaptive immunity. They

can phagocytose particulate antigens,

present allergens to T cells.2,3

They also regulate lung homeostasis

by releasing both pro- and

anti-inflammatory cytokines when

activated by cytokines or allergen

binding to IgE receptors.4

ILC2s appear to be involved in both

adaptive and innate immunity. They

respond to both antigens and

epithelial signals like IL-33, IL-25 and

TSLP.5,6

ILC2s direct Th2 responses around

airway remodelling and repair. They

also release IL-5 and IL-13, which

recruit eosinophils and stimulate

mucus hypersecretion and airway

hyperreactivity.5,6


1. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA; 2. Brusselle GG, Maes T, Bracke KR. Nat Med

2013;19(8):977-9; 3. Barnes PJ. Chapter 254: Asthma in Harrison’s Principles of Internal Medicine. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015; 4. Vijverberg SJ, Hilvering B,

Raaijmakers JA, Lammers JW, Maitland-van der Zee AH, Koenderman L. Biologics 2013;7:199-210. doi: 10.2147/BTT.S29976; 5. Chang YJ, DeKruyff RH, Umetsu DT. J Leukoc Biol 2013;94(5):933-40.


Goblet cells in the epithelial layer secrete

mucus into the airway. Many asthma

patients’ airways contain mucus plugs,

which are the result of mucus

hypersecretion and goblet cell metaplasia.2-5

Smooth muscle cells around the bronchial

airway respond to a variety of mediators

during the asthmatic inflammatory response.

When they contract, bronchoconstriction

occurs.1,2


How severe asthma differs from milder forms


1. Kumar RK, Jeffery PK. Pathology of Asthma. In: Adkinson NF, et al. (eds) Middleton's Allergy Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p986; 2. Barnes PJ. Chapter 254: Asthma. In:

Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015; 3. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al.

(eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812; 4. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73.

How is severe asthma different from milder forms of

asthma?

Many mild or moderate exacerbations

are amplified in severe asthma1

Inflammation and remodelling

processes become increasingly

involved as asthma becomes more

severe and chronic2,3

Inflammatory profile can also

indicate disease severity, e.g.

asthma severity is associated with the

simultaneous presence of eosinophils

and neutrophils in the lungs4

Distinguishing asthma by

phenotyping may better identify

the best therapeutic options for

severe asthma patients as it

considers both the clinical and

pathophysiologic components of the

disease4


What is an asthma phenotype?

1. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73.

It is increasingly evident that severe asthma is not a single disease - therefore the

concept of asthma phenotyping has emerged1

A phenotype is defined as a set of observable characteristics

resulting from interaction between genetics and the environment1

These phenotypes should evolve into asthma endotypes, which combine clinical

characteristics with identifiable mechanistic pathways1


Risk factors for asthma and severe asthma, and those that

are common to both

IL, interleukin.

1. Barnes PJ. Chapter 254: Asthma. In: Asthma in Harrison’s Principles of Internal Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015; 2. Jarjour NN, Erzurum SC,

Bleecker ER et al. Am J Respir Crit Care Med 2012;185(4):356-62; 3. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73; 4. Chanez P, Wenzel SE, Anderson GP et al. J Allergy Clin Immunol

2007;119(6):1337-48; 5. Kozyrskyj AL, Kendall GE, Jacoby P et al. Am J Public Health 2010;100(3):540-6.

Many mild and moderate asthma risk factors are also the same for severe asthma:1-5

Risk factors for all asthma severities

Atopy1,2

Airway hyperresponsiveness1,2

Gender (female sex in adult-onset asthma and male sex in childhood asthma)2-4

Ethnicity (susceptibility linked to ethnic-specific genetic variations)1

Lower socioeconomic position5

Obesity1-4

Indoor/outdoor allergens1

Occupational exposure1,3

Tobacco smoke1-3

Respiratory infections1,3

Additional associations for severe asthma

Genetic factors (e.g. genetic variation in IL-4 and IL-6 receptor)3,4

Older age at onset of asthma3

Disease duration3

Exacerbations3

Inflammatory characteristics (eosinophilic and neutrophilic)3

Reduced responsiveness to therapy for asthma3


Exacerbations in severe asthma

1. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812; 2. Kumar RK, Jeffery PK. Pathology of

Asthma. In: Adkinson NF, et al. (eds) Middleton's Allergy Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p986; 3. Barnes PJ. Chapter 254: Asthma. In: Asthma in Harrison’s Principles of Internal

Medicine. 2012. Available at: http://accessmedicine.mhmedical.com/. Last accessed November 2015; 4. Kupczyk M, ten Brinke A, Sterk PJ et al. Clin Exp Allergy 2014;44(2):212-21; 5. Chung KF, Wenzel SE, Brozek

JL et al. Eur Respir J 2014;43(2):343-73; 6. Miller MK, Lee JH, Miller DP, Wenzel SE; TENOR Study Group. Respir Med 2007;101(3):481-9.

• Asthma patients can experience periodic flare-ups known as exacerbations1

• They consist of acute or subacute episodes of progressively worsening

shortness of breath, coughing, wheezing and chest tightness1

- They are more common in patients with severe asthma3,4

• Exacerbation frequency and severity can be used as a measure of disease5

• Previous exacerbations are a strong predictor of future risk6

- In one study, patients with a recent severe exacerbation were six times more likely to

experience a future severe exacerbation than those without6

The rate of exacerbations was five times higher in patients with severe

asthma versus those with mild-to-moderate asthma (1.2 vs. 0.24

exacerbations per patient per year, respectively)5


Remodelling and airway obstruction

FEV1, forced expiratory volume in 1 second.

1. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73; 2. Jarjour NN, Erzurum SC, Bleecker ER et al. Am J Respir Crit Care Med 2012;185(4):356-62; 3. Holgate ST, Sly PD. Asthma

Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p812.

• The airway epithelium is thicker in severe asthma than it is in mild-to-moderate

asthma1

• In lung function studies, the correlation of airway wall thickness and FEV1

suggests that airway remodelling contributes to airway obstruction in severe

asthma2

• Altogether, airway obstruction may result from a combination of:3

- Bronchoconstriction as a consequence of active airway smooth muscle contraction

- Airway wall thickening associated with inflammation and remodelling

- Luminal obstruction caused by mucus hypersecretion, which may also be thickened due

to dehydration

• Chronic airway obstruction can lead to airway closure or uneven ventilation1


Summary


1. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries,

1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743-800; 2. World Health Organization. Available at: http://www.who.int/gard/publications/

GARD%20Book%202007.pdf. Last accessed November 2015; 3. To T, Daly C, Feldman R, McLimont S. BMC Public Health 2012;12:293. doi: 10.1186/1471-2458-12-293; 4. Luskin AT, Chipps BE, Rasouliyan L

et al. J Allergy Clin Immunol Pract 2014;2(5):544-52.e1-2. doi: 10.1016/j.jaip.2014.02.011; 5. Serra-Batlles J, Plaza V, Morejón E et al. Eur Respir J 1998;12(6):1322-6; 6. Accordini S, Corsico AG, Braggion M et

al. Int Arch Allergy Immunol 2013;160(1):93-101; 7. Sullivan SD, Rasouliyan L, Russo PA et al. Allergy 2007;62(2):126-33; 8. Kumar RK, Jeffery PK. Pathology of Asthma. In: Adkinson NF, et al. (eds) Middleton's

Allergy Principles and Practice. 8th ed. Saunders Elsevier, PA, USA: 2014. p986; 9. Holgate ST, Sly PD. Asthma Pathogenesis. In: Adkinson NF, et al. (eds) Middleton's Allergy: Principles and Practice. 8th ed.

Saunders Elsevier, PA, USA: 2014. p812; 10. Chung KF, Wenzel SE, Brozek JL et al. Eur Respir J 2014;43(2):343-73.

• An estimated 242 million people are affected by asthma in some form1

- It causes 250,000 deaths annually2,3

• Asthma can have a significant impact on QoL, with severe asthma impacting

more greatly than milder forms4

• Total severe asthma costs are estimated to be five times those of milder forms5

- As asthma control decreases, economic costs increase6,7

• In general, asthma’s manifestations are related to airflow obstruction and airway

hyperresponsiveness8

- Develops from complex interactions between environmental exposures and genetic

predispositions9

- Exacerbations can be used as a measure of disease severity10

• Distinguishing asthma by phenotyping may provide better options for treatment10


Documents

Module 1 - GSKpro · 2018. 3. 21. · Accordini S, Corsico AG, Braggion M et al. Int Arch Allergy Immunol 2013;160(1):93-101; 6. Antonicelli L, Bucca C, Neri M et al. Eur Respir J