11

Inspiring

ChangeA fresh look

at asthmaMedia resource

This booklet is intended for non-US/UK healthcare journalists

Inspiring

Change

Foreword

22 33

Five quick tips to help you get the most out of this booklet:

2 3

Vivienne ParryScience and healthcare journalist

I suspect that we all thought that asthma was a done

deal, that there were no more innovations to be had in

the field. However, this is not the case; there is, in fact,

a significant unmet medical need. Despite current

treatment options, almost one in two people with

asthma still have symptoms and are at risk of asthma

exacerbations so could benefit from new treatment

options. As a healthcare journalist and broadcaster,

I always need a breadth of information about the disease

area I am covering so that I can be confident my report

is accurate. This media resource provides exactly that

information for those interested in asthma.

Professor William Busse Department of Medicine, University of Wisconsin

I have worked in the area of asthma for more than 40

years; the evolution in treatment over that time has been

amazing. Recently the recognition that asthma is not one

disease, but many diseases with different characteristics,

has opened up a whole new vista for more effective and

more personalised treatments for patients. This media

resource dives into this area. I hope what you come

away with is a sense that we are seeing a new era of

management and treatment to address the clear need to

continue to improve outcomes for patients with asthma.

Discover Looking to satisfy your curious mind and learn more about what’s new in asthma therapy? Jump straight to the innovations in asthma treatment section

View Interested in hearing a respiratory expert’s opinion? Look out for the videos included throughout the booklet. Are you reading this in paper form? Just scan the QR code and enjoy!

Understand Looking for a definition? Go to the back of the booklet to read a glossary of key terms

Consider Reviewing respiratory clinical trial data? Read the key questions to consider when reviewing and reporting on clinical trial results

Browse Looking for further asthma information? Visit www.newshome.com to access a wealth of up-to-date and useful information on asthma

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Contents

The facts you need to know about asthma

About asthma• What is asthma?

• What are exacerbations?

• What is the economic impact of asthma?

• What is the patient and physician perspective?

Asthma management • How is asthma control defined?

• How is asthma treated?

• When should a patient’s treatment be reviewed?

• What are the latest treatment innovations?

• What are the latest innovations in personalised treatments and self-management?

Interpreting asthma clinical trials

• How are symptoms and lung function evaluated?

• What are the endpoints of an asthma trial?

• Some asthma clinical trials are designed to more accurately represent clinical practice. What does this mean?

• How should inhaler patient preference data be interpreted?

Questions to consider when reviewing clinical trial data

Glossary of key terms

References

6

8

14

20

24

26

28

66 77

The facts you need to know about asthma

Some of the words

people with asthma use to describe how

they feel:

New asthma treatments and

approaches are required to address the current unmet

medical need in asthma. The long-term goals of

asthma management are to achieve good symptom control, and to minimise future risk of exacerbations, fixed airflow limitation and side-effects

of treatment.6

Embarrassed

Anxiety

Fear

In the shadow of

asthma

Blamed

Symptomatic asthma patients have ~x6

greater chance of having an asthma attack in the

next few weeks than those with minimal to no

daytime symptoms.5

To help identify patients who are still

symptomatic on treatment, physicians should proactively ask their patients questions

about their asthma symptoms. In addition, patients should seek

medical attention if they have any night-time symptoms, or if their symptoms don’t

respond to treatment.

Asthma is seen as easy to manage and the misperception may exist that people with asthma

symptoms can lead a normal life.

This media resource is bursting at the seams with important information about asthma. However, here are the key things to remember about this disease.

Despite current treatment options, almost one in two

people with asthma still have symptoms1,2,3 and may experience frightening and potentially life-threatening

asthma exacerbations. These patients could

benefit from new treatment options.4

88 99

About asthma

What is asthma?

Asthma is a chronic disorder of the airways characterised by airway inflammation and bronchoconstriction.

Asthma is a chronic disorder of the airways

characterised by airway inflammation and

bronchoconstriction. When a person with asthma

comes into contact with an asthma trigger (e.g. viral

infection, pollen, smoke, exercise), their airways can

become more inflamed, swollen and constricted and

produce excess mucus. These reactions cause the

airways to become narrower and irritated, making

it difficult to breathe.6,7

Inflammation in asthma is associated with:6

• exaggerated bronchoconstriction

• symptoms (breathlessness, wheezing,

cough and chest tightness)

• variable airflow limitation

• reduced lung function.

There is no single cause of asthma, but certain

factors may increase the likelihood of developing it,

including genetic and environmental factors.8

The scale of the unmet need in asthma

Asthma often results in a decline in physical activity

and the disruption of people’s ability to lead a full life,

interfering with everyday tasks and participation in

family routines.8,9

People with asthma can feel frustrated, embarrassed,

blamed – like they’re living in the shadow of asthma.

Asthma symptoms and exacerbations are associated

with a poor quality of life10,11 and have a significant

impact on people with asthma:

• sleeplessness8

• daytime fatigue8

• reduced activity level8

• work absenteeism (missed time at work)8

• interference with normal day-to-day activities9

• increased anxiety9

• fear of being hospitalised9

• affects the course of the disease.12

Asthma exacerbations can make people with asthma

feel deflated over a battle they feel can never be won.

Despite current treatment options, almost one in two

people with asthma still have symptoms1,2,3 and could

benefit from new treatment options.4

Click here to view the video or scan the QR code

Expert insights on the impact of asthma on patients’ lives

Professor David Halpin, Consultant in Respiratory

Medicine, Royal Devon and Exeter Hospital, UK,

talks about how asthma can impact patients’ lives.

How is asthma diagnosed?

A clinical diagnosis of asthma may be confirmed by measurements of lung function to assess:6

• the severity of airflow limitation (due to

bronchoconstriction and inflammation)

• its reversibility with the use of a short-acting

inhaled bronchodilator therapy

• the variability in airflow limitation.

The onset of asthma symptoms are often triggered

by allergens, so physicians often measure a patient’s

allergic status to identify risk factors to avoid.6

How many people worldwide are affected by asthma?

As many as 300 million people worldwide may have asthma, including a growing number of adults.7

Despite current treatment options, almost 1 in 2 people with

asthma still have symptoms.1,2,3

Fast fact

QA

Q

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QA

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EU IT ES ES FR SE CA CA USA US US US (p) NW-A

Almost 1 in 2 people with asthma still have symptoms

symptoms

co

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airwayslung function

chronic

bronchodilation

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breathlessnessbronchoconstriction

exacerbationsanti-inflammatoryinflammation

wheezing

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1010 1111

About asthma

In clinical practice exacerbations are identified as

events characterised by a change from the patient’s

previous status.13

Asthma exacerbations are medically defined as

a deterioration of asthma symptoms that requires

initiation or at least a doubling of systemic

glucocorticoids for ≥3 days.14

Asthma exacerbations are:

• potentially life threatening15

• scary for patients.9

Severe asthma exacerbations are defined as events

requiring urgent action on the part of the patient

and physician to prevent a serious outcome such as

hospitalisation or death, and in clinical trials include:15

• Use of systemic corticosteroids (tablets, suspension,

or injection), or an increase from a stable

maintenance dose, for at least three days

• A hospitalisation or emergency room visit because

of asthma requiring systemic corticosteroids.

Asthma symptoms and exacerbations are associated

with a poor quality of life.10,11 In addition, asthma

exacerbations affect the course of the disease.12

There is an association between symptomatic asthma

and future severe asthma-related healthcare events.16

Asthma exacerbations can also be costly to healthcare

systems due to the need for emergency care.17

Asthma exacerbations

are common and

can be potentially life threatening.9

What are exacerbations?

People suffering from asthma experience recurrent episodes of wheezing, breathlessness, chest tightness and coughing. These episodes may be punctuated by periods of more severe and sustained worsening in symptoms called asthma exacerbations.6,7

The reasons why patients continue to experience symptoms on current standard treatment include:

• Poor inhaler technique

• Poor adherence to therapy

• Limitations of currently available therapies

• Not understanding and/or unable to avoid the

environmental triggers

• Miscommunication between patients and physicians

• Not responding to medications.

The reasons why patients continue to experience symptoms on current standard treatment include:A

Q

Miscommunication between patients

and physicians

Poor adherence to therapy

Not responding to medications

Not understanding and/or able to

avoid the environmental triggers

Poor inhaler technique

Limitations of currently available therapies

X

1212 1313

About asthma

Most patients have low

expectations of what can be

achieved by asthma management

and do not realise their condition

can be improved.4 Many patients

are resigned to the effects of poor

asthma control until made aware

that the impact of their symptoms

can be improved through revisiting

their treatment plan.4

Asthma is seen as easy to manage

and the misperception may

exist that people with asthma

symptoms can lead a normal life.

Having symptom free days has

been found to be the most

important aspect for people

with asthma.19

Above-left: Both patients and

physicians tend to overestimate the

degree of control achieved

Left: Patient and physician perceptions

of asthma symptom control are often

not aligned

A

What is the patient and physician perspective on the expectations of asthma management?

Patients and their physicians often underestimate the level of asthma symptom management and their perceptions of it are often not aligned.18

Telephone (n=52) and mail (n=411) surveys were conducted with a random sample of Canadian primary care and specialist physicians (respirologists or internists who had reported a

subspeciality in respirology) who were currently treating patients with asthma (n=463).

QA

What is the economic impact of asthma exacerbations?

Asthma exacerbations can result in significant direct and indirect medical costs.

The economic costs associated with asthma are

estimated to rank as one of the highest among

chronic diseases. Developed economies can expect

to spend up to 2% of their healthcare budget

on asthma.11 Globally, the costs associated

with asthma are estimated to exceed those of

tuberculosis and HIV/AIDS combined.20

Click here to view the video or scan the QR code

Expert insights on the underestimation of the burden of asthma

Professor Eric Bateman, Professor of Respiratory

Medicine at the University of Cape Town, South

Africa, talks about why the burden of asthma is

underestimated and the unmet medical need in

the treatment of the disease.

Up to 300 million people worldwide may have

asthma7 and around 30 million people in Europe.21

Fast fact

QP

erc

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tag

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Doctor objective assessment(using the EPR-3 criteria)

USA CHOICE survey510 patients reporting controller use

Patient subjective assessment(self-reported)

50

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0Well Not well Very poorly

50

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0Completely Well Somewhat Poorly or not

85% of patients were NOTachieving goal of treatment

Only 6% believed they arepoorly controlled

Perc

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Actual(based on Canadian Asthma Consensus

Guideline)

Patients GPs

Perceptions

Specialists

Controlled

Not controlled

53

47

10

90

12

88

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Up to 300 million people

1414 1515

Asthma management

QA

How is asthma control defined?

The Global Strategy For Asthma Management And Prevention (GINA) report 2014 defines asthma control as:6

How is asthma treated?

The long-term goals of asthma management are to achieve good symptom control, and to minimise future risk of exacerbations, fixed airflow limitation and side-effects of treatment.6

• Minimal to no daytime asthma symptoms

• No limitations on activities

• No nocturnal symptoms or awakenings

• Minimal to no need for reliever or rescue therapy

• Normal lung function (FEV1 or PEF)

• No exacerbations.

Targeting inflammation is the foundation of treatment

strategies for asthma. The current standard treatment

for asthma includes inhaled corticosteroids (ICS),

which treat the underlying inflammation. However,

the heterogeneity of asthma and responsiveness to

therapy necessitates a management approach that

uses treatments with complementary modes

of action (MOAs). ICS can therefore be combined

with other maintenance therapies with different

MOAs. The most commonly prescribed drug used

in addition to maintenance ICS therapy is a long-

acting beta-2 agonist bronchodilator (LABA) which

has proven to be an effective treatment option in

patients symptomatic on maintenance ICS alone.6

Step 1 Step 2 Step 3 Step 4 Step 5

Asthma education, environmental control

As-needed rapid-acting ß

2-agonists

As needed rapid-acting ß2-agonists

Controller options

(reliever treatments include inhaled anticholinergics, short-acting oral

ß2-agonists, some LABAs and short-

acting theophylline)

Select one Select oneTo Step 3 treatment, select one or more

To Step 4 treatment, add either

Low-dose ICSLow-dose ICS plus

LABAMedium-or high-dose

ICS plus LABA

Oral glucocorticosteroid

(lowest dose)

Leukotriene modifier

Medium-or high-dose ICS

Low-dose ICS plus leukotriene modifier

Leukotriene modifier Sustained-release

theophylineAnti-IgE treatment

Low-dose ICS plus sustained release

theophylline

ICS/LABA has become the current standard treatment for the majority of patients with asthma. Pivotal data (in patients ≥12 years old) show that, compared with maintenance ICS alone, bronchodilation therapy with LABAs added on to ICS:22

A

Q

Reduced the number of

exacerbations

Improved

lung function

Decreasedrescue inhaler use

Improved symptoms

1616 1717

Asthma management

When should a patient’s treatment be reviewed?

Without pro-active intervention by the physician, asthma patients invariably do not alter their behaviour in relation to symptoms, or even in response to exacerbations resulting in a visit to the hospital or emergency department.

The Royal College of Physicians in the UK has developed three questions (RCP3Qs) as a practical tool to detect continued asthma symptoms:23

New asthma treatments and

approaches to treatment are

required to address the current unmet medical need in asthma

in order to minimise symptoms,

reduce risk of exacerbations,

delay the time to an exacerbation

and improve quality of life.

Fast fact

QA

The RCP3Qs reliably quantify current asthma control,

with a negative response to all three questions

indicating good control.24 Due to their simplicity,

the RCP3Qs are a good tool for use by physicians in

day-to-day practice25 to proactively identify whether

patients are still experiencing asthma symptoms.

An asthma patient should seek medical attention if

they have any night-time symptoms, especially

nocturnal wakening, or if symptoms do not respond to

increased use of inhaled ß2-agonist therapy. Peak flow

measurements are also important because studies have

suggested that many asthma patients are unable to

reliably detect deterioration in their lung function

from their subjective perception.26,27

An asthma patient should seek

medical attention if they have any

night-time symptoms.

In the last month/week have you had difficulty sleeping due to your asthma (including cough symptoms)?

Have you had your usual asthma symptoms (e.g. cough,

wheeze, chest tightness, shortness of breath) during the day?

Has your asthma interfered with your usual daily activities (e.g. school, work, housework)?

1

2

3

minimisesymptoms

minimisesymptoms

reduce the risk of exacerbations

delay the time to

exa

ce

rbati

ons

Improvequalityof life

1818 1919

Asthma management

What are the latest innovations in asthma treatment?

Anti-cholinergic bronchodilators:

Airway narrowing in asthma occurs as the result

of airway smooth muscle contraction, oedema,

thickening of the airway wall (re-modelling), and

an increased secretion of mucus.28 By relaxing the

smooth muscle in the airways, bronchodilators

may be effective in relieving or preventing

asthma symptoms.

Treatment guidelines recommend the addition of a

LABA bronchodilator as an effective treatment option

in patients symptomatic on a maintenance ICS alone.6

Spiriva® (tiotropium) Respimat® is an inhaled

long-acting, anticholinergic bronchodilator newly

indicated for use in the treatment of asthma. No new

inhaled treatment class has been approved in asthma

for nearly a decade.

It is indicated as an add-on maintenance

bronchodilator treatment in adult patients with asthma

who are currently treated with the maintenance

combination of inhaled corticosteroids(≥800 µg

budesonide/day or equivalent) and long-acting ß2

agonists and who experienced one or more severe

exacerbations in the previous year.

This new indication is based on the UniTinA-asthma®

large-scale, Phase III clinical trial programme which

investigated adults with asthma who continued to

have symptoms despite taking at least ICS therapy.

Pivotal, Phase III study results demonstrated that for

patients who still have symptoms despite treatment

with current standard treatment (ICS/LABA), the

addition of Spiriva® Respimat®:

• Increased the likelihood of patients improving

control of their asthma symptoms by 68%29

• Significantly reduced the risk of patients having a

severe asthma exacerbation by around a fifth (21%)14

• Significantly reduced the risk of a patients’ asthma

worsening by around a third (31%)14

• Delayed time to patients’ first severe asthma

exacerbation and first episode of asthma worsening.14

These studies are designed to more accurately

represent clinical practice; therefore patients receive

investigational compounds in addition to their

standard medication. This may make outstanding

clinical trial results more difficult to achieve in contrast

to comparing new compounds with placebo only, so it

is interesting to note that the results achieved in these

studies translate into true patient benefits.

Spiriva® Respimat® works by opening airways and

helping to keep them open for at least 24 hours.30,31,32

New biologics:

Omalizumab was the first humanised monoclonal

antibody licensed to treat asthma. Targeting the

immunoglobulin IgE, omalizumab has proved effective as

a treatment for patients with severe allergic asthma33,34

by reducing the numbers of eosinophils in the airways.34

Administered as a subcutaneous injection, omalizumab

has been largely reserved as a treatment for patients with

severe allergic asthma.

New biological treatments currently being investigated

include monoclonal antibodies targeting interleukin-5

(IL-5) and interleukin-13 (IL-13).

• Recent studies have shown that mepolizumab

therapy, which targets IL-5, is an effective and well

tolerated treatment that reduces the risk of asthma

exacerbations in patients with severe eosinophilic

asthma.35 Other monoclonal antibodies targeting

IL-5 that are in development include benralizumab

and reslizumab.

• Monoclonal antibodies targeting IL-13 in

development include lebrikizumab,

dupilumab and tralokinumab.

Personalised treatments and self-management:

Asthma is classified as a complex genetic disease with its

pathogenesis and severity determined by the interaction

of many genes and environmental factors. As asthma

is a heterogeneous disease, treatment choice can be

individualised according to a patient’s type of asthma.6

Pharmacogenetic approaches hold the promise of

matching individualised treatments to specific

genotypes in a way that minimises side effects while

improving therapeutic outcomes to offer personalised

asthma management.

There has been some progress in the past five years with

large prospective studies to identify genes that influence

treatment response. These, however, need further

replication and validation.

Significant reduction in time to first severe asthma exacerbation - pooled Phase III

Patients at riskPlacebo Respimat®

Tiotropium Respimat®

Add-on to ICS+LABA

454 435 412 388 379 367 356 339 332 319 303 290 282 272

453 430 409 401 389 378 363 353 348 339 331 319 308 298

Time (days)

Pati

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ith

at

least

on

e s

eve

re

ast

hm

a e

xace

rbati

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(%

)

HR=0.79; Risk reduction of 21% (P=0.03)

Tiotropium Respimat® n=122 (26.9%), Placebo Respimat® n=149 (32.8%)

Tiotropium Respimat®: 282 days; Placebo Respimat®: 226 days (25th percentile)

Number needed to treat: 15

Placebo Respimat®

Tiotropium Respimat®

50

40

30

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0 25 50 75 100 125 150 175 200 225 250 275 300 325

Omalizumab has

proved effective as a treatment for patients with severe allergic asthma.33,34

Developed countries can expect to

spend up toof their healthcare budget on asthma.11

QA

Fast fact

2%

2020 2121

Interpreting asthma clinical trials

Fast fact

Lung function:

Lung function is measured

by spirometry or peak

expiratory flow.

Spirometry

Spirometry measures:

a) FEV1 (forced expiratory volume in one second ) –

the volume of air (in litres) exhaled in the first second

when the patient inhales fully and exhales with as

much force, and as quickly, as possible

b) FVC (forced vital capacity) – the total volume of

air (in litres) exhaled when the patient inhales fully

and exhales completely with as much force, and as

quickly, as possible.

The FEV1 /FVC ratio is normally greater than 0.75-0.80

(0.90 in some children). Values less than these figures

suggest airflow limitation which indicates that the patient

may be suffering from asthma.6

Peak expiratory flow

Peak flow measurements may be taken using a portable

meter into which the individual breathes as hard and as

fast as he or she can, taking the highest

of three consecutive readings

A diagnosis of asthma is suggested by:6

a) history of respiratory symptoms such as wheeze,

cough, shortness of breath and chest tightness that

typically vary over time and in intensity

b) symptoms worse at night or on waking, and often

triggered by viral infections, exercise, exposure to cold

air and allergens

c) FEV1/FVC <0.75-0.80 in adults (<0.90 in children)

d) variable limitation in airflow when breathing out

(examples below) with the greater the variation, or

the more occasions excess variation is seen, the more

confident the diagnosis

i. Increase in FEV1 >12% (and 200ml) from baseline

10-15 minutes after inhalation of a short-acting

inhaled bronchodilator

ii. Average daily morning-evening variation in peak

flow >10% in adults (>13% in children).

Click here to view the video or scan the QR code

Clinical trials video

This video provides an overview of the process of

clinical trials and the phases of drug development.

Before a medicine is made available to patients,

rigorous testing of a potential compound must

be carried out over many years in the laboratory.

After pre-clinical testing, clinical studies are carried

out to assess the safety, tolerability, efficacy and

suitable dosage of a treatment.

Symptoms:

There are several validated tools that can be used

to measure asthma symptoms and quality of life

(QoL) in adult and paediatric patients with asthma.

These include:

• Standardised Asthma Quality of Life Questionnaire

(AQLQ) – measures work-related activities, social

activities, sleep, and strenuous and moderate

exercise in adults with asthma

• Asthma Control Questionnaire (ACQ) – measures

changes in nocturnal awakenings, morning

symptoms, activity limitations, shortness of

breath/wheezing and rescue inhaler usage in

adults and children with asthma

How are symptoms and lung function evaluated?

• Asthma Control Test (ACT) – measures asthma

control via a simple five-point questionnaire,

which is self-completed by patients

• Paediatric Asthma Quality of Life Questionnaire

(PAQLQ) –measures functional problems (physical,

emotional and social) that children with asthma

have identified as troublesome in their daily lives.

Patient-reported outcomes, such as health-related

quality of life (HRQoL) data or an index of the

patients’ breathlessness (dyspnoea), are used in

clinical trials to provide insight into the practical

consequences of asthma treatment.

Asthma symptoms are associated with a poor quality of life.10,11 Having symptom free days has been found to be the most important aspect for people with asthma.19

10080

7060

5040302010

0

QA

2222 2323

Interpreting asthma clinical trials

What are the key endpoints of an asthma clinical trial?

FEV1 is a primary endpoint for studies of bronchodilator therapy for the treatment of asthma.

Measurement of peak flow can also be used to evaluate asthma control.

FEV1 is preferable to peak flow as a measure in

asthma clinical trials.13

Asthma control refers to the extent to which

symptoms have been reduced or removed by

treatment.36 Asthma control is assessed by looking

at current clinical control along with an evaluation

of future risk.13

There is currently no universally recognised ‘‘gold

standard’’ for the measurement of asthma control.

Of the 17 different asthma control composite score

instruments only two (ACQ and ACT) have been

selected as core measures for clinical research

initiated by the National Institutes of Health (NIH).37,38

These questionnaires are able to provide

an insight into patients’ perception of

their condition alongside

objective measurements of

asthma control.13

Q

A Conducting asthma clinical trials designed to more accurately represent clinical practice means that the patients are allowed to take their standard asthma medication (although this can’t include a drug from the same class as the investigational drug) in addition to being randomly allocated either the investigational drug or a placebo.

Some asthma clinical trials are designed to more accurately represent clinical practice. What does this mean?

It is important to be careful not to compare efficacy

data from trials where standard therapy is allowed

with those clinical trials comparing new compounds

with placebo only. When an investigational drug

is being compared to placebo alone without any

other standard treatments its efficacy is likely to be,

proportionally, much greater.

How should inhaler patient preference data be interpreted?

Inhaler preference is now recognised as a valid patient-reported outcome in asthma clinical studies.39

However, most patient preference questionnaires

have been developed without input from patients

or experts in psychometric testing and this lack

of precision with measurement can make device

preference literature very difficult to interpret.38

In designing a rigorous inhaler satisfaction/

preference trial, an important factor is the use of

a reliable and valid inhaler satisfaction/preference

measurement tool.40

In a recent review of 30 published inhaler preference

studies, only two studies were found to have used

robust instruments for measuring preference

and satisfaction: the Patient Device Experience Assessment (PDEA) and the Patient Satisfaction

In a recent review of 30 published inhaler preference

studies, only two studies were found to have used robust

instruments for measuring

preference and satisfaction.

and Preference Questionnaire (PASAPQ); both

developed by experts in psychometric testing and

subjected to field testing. Of these, only the PASAPQ

has a published validation.39

Some reasons why patients may still experience symptomatic asthma and exacerbations include:

Most patients have low expectations of what can be achieved by asthma management and do not realise that their condition can be improved.4

Fast fact

Q QA A

There is currently no universally recognised ‘‘gold standard’’ for the measurement of asthma control.

Poor inhaler technique

Limitations of currently available therapies !!!

Poor adherence to therapy

2424 2525

Questions to consider when reviewing clinical trial data

Clinical relevance

Were all clinically relevant outcomes reported?

What is the impact on quality of life?

What is the patient benefit?

What do the results mean for the wider patient

population and for the healthcare community?

Validity

How were patients selected for the study?

Is there a potential for bias?

Were the patients randomly assigned to

treatment groups?

• Random assignment to treatment groups

avoids procedure selection bias

Were all of the patients who entered the

study accounted for at its conclusion? If

some patients are missing from the study

conclusion, are the results still significant?

Were the investigators and the patients

blinded as to who received which treatment?

Were the groups treated similarly in all respects

other than the treatment they received?

How precise is the estimate? Check the

confidence intervals (CI)/p-value/hazard ratio

• Investigators most frequently use a 95% CI

2626 2727

Glossary of key terms

Symptoms and exacerbations

Symptomatic asthma: symptoms of asthma include

episodes of wheezing, breathlessness, chest tightness and

coughing.6 Despite current treatment options, almost

one in two people with asthma still have symptoms.1,2,3

Exacerbations: exacerbations are a worsening of asthma

symptoms. Medically they are defined as a deterioration

of asthma symptoms that requires initiation or at least a

doubling of systemic glucocorticoids for ≥3 days.14

Asthma exacerbations are associated with a poor quality

of life for patients and are potentially life threatening.10,11

They can affect the course of disease12 and can be

costly in terms of emergency care.17

Reliever and maintenance therapy

Reliever therapy6: treatment taken to improve asthma

symptoms quickly. The reliever inhaler usually contains

a short-acting bronchodilator which widens the airways

and makes it easier to breathe again.

Maintenance therapy6: prescribed to reduce the risk

of asthma exacerbations or delay the time before an

exacerbation occurs. These preventer treatments reduce

inflammation and irritation of the airways. The most

commonly prescribed maintenance treatments are ICS

either alone or in combination with a LABA (ICS/LABA).

Bronchodilation

Bronchodilation: the process by which narrowed airways

are opened and kept open. Airway narrowing in asthma

occurs as the result of airway smooth muscle contraction,

oedema, thickening of the airway wall (re-modelling) and

increased secretion of mucus.

Bronchodilators: a key component of treatment for

people with asthma, bronchodilators relax the muscles

surrounding narrowed airways to allow them to open

more widely. Treatment guidelines recommend the

addition of a LABA bronchodilator as an effective

treatment option in patients who remain symptomatic on

maintenance ICS alone. However, many patients continue

to have symptoms on at least ICS/LABA therapy.

Targeting inflammation

Inhaled corticosteroids (ICS): the foundation of asthma

treatment. By controlling airway inflammation and

reversing structural changes in the airway walls, ICS

treatment aims to control asthma symptoms and reduce

the risk of exacerbations.

Oral corticosteroids: a short course of oral corticosteroids,

typically for 7-11 days, is effective in treating a severe

exacerbation. Once the acute inflammation of the airways

has improved with treatment, most asthma patients are

able to return to their previous medication.

Other prescribed asthma treatments

Leukotriene receptor antagonists: treatments which

block the action of naturally occurring chemicals in the

lungs, called leukotrienes, which can lead to inflammation

in the airways. Leukotriene receptor antagonists are

indicated for the prevention of exercise-induced asthma.

Monoclonal antibodies: a category of treatments used

to target the acute inflammatory response associated

with asthma by blocking the action of Immunoglobulin E

(IgE). In asthmatics, IgE released in response to allergens,

prompts the release of histamine and other substances

which initiate the cascade of inflammatory symptoms

(bronchoconstriction, mucus production, wheezing

and shortness of breath). Monoclonal antibodies are

recommended in people with severe persistent allergic

asthma who suffer frequent severe exacerbations

requiring emergency treatment or hospital admission.

Theophyllines: taken orally, theophyllines have

anti-inflammatory, immunomodulatory and

bronchoprotective effects that potentially contribute

to their efficacy as a preventative anti-asthma treatment.

Clinical trials

Forced expiratory volume in one second (FEV1): the

maximum volume of air that can be forcibly expired in

one second, following maximal inspiration. FEV1 is reduced

in both obstructive and restrictive respiratory diseases.

Percentage forced expiratory volume (FEV1%): the FEV

1

as a percentage of a normal value calculated based on

the person’s age, sex, height and race.

Forced vital capacity (FVC): the lung volume a person

can expel forcibly after a maximum inspiration, leaving

only the residual volume.

Hazard ratio (HR): a summary of the difference between

two survival curves, representing the reduction in the risk

of death on treatment compared to the control. It is also

used to calculate the degree of improvement in the trial’s

endpoint (e.g. overall survival, progression-free survival)

over the course of the entire study.

Confidence intervals (CIs): CIs provide information about

the range of treatment effects. The wider the interval,

the more variable the result and the less likely it is to be

close to the true value that would be generated when

all eligible patients were tested. Investigators most

frequently use a 95% CI.

2828 2929

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Notes

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Inspiring

Change

Last updated September 2014