Asthma in Adults: The Right Clinical Information, Right Where It's Needed

Asthma in adults
The right clinical information, right where it's needed
Last updated: Jan 29, 2018

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Prevention 6
Secondary prevention 6
Diagnosis 7
Case history 7
Step-by-step diagnostic approach 7
Risk factors 8
History & examination factors 9
Diagnostic tests 10
Differential diagnosis 12
Diagnostic criteria 15
Treatment 17
Step-by-step treatment approach 17
Treatment details overview 19
Treatment options 22
Emerging 43
Follow up 44
Recommendations 44
Complications 44
Prognosis 45
Guidelines 47
Diagnostic guidelines 47
Treatment guidelines 47
Evidence scores 49
References 51
Disclaimer 59
Summary
◊ Patients present with recurrent episodes of shortness of breath, chest tightness, wheezing, or
coughing.
◊ Examination typically demonstrates an expiratory wheeze; however, in severe asthma there is poor
air entry and the chest is silent.
◊ Treatment is step-wise, based on symptoms. Patients may need to monitor their peak expiratory flow
daily and should be aware of the warning signs of a severe attack.
◊ Some patients may develop progressive, irreversible obstructive lung disease.

Asthma in adults Basics
Definition
Asthma is a chronic inflammatory airway disease characterised by intermittent airway obstruction and hyper-
reactivity. Many cellular components are involved in the asthmatic pathway, including mast cells, eosinophils,
BASICS
T lymphocytes, macrophages, neutrophils, and epithelial cells. On insult, in susceptible people, inflammation
causes increased bronchial hyper-responsiveness and recurrent episodes of wheezing, breathlessness,
chest tightness, and coughing, which are usually associated with widespread but variable airway obstruction
that is reversible either spontaneously or with treatment.[1]
Epidemiology
Asthma affects approximately 30 million people in Europe and more than 25 million people in the US.[2] [3]
The global burden is reported to be 300 million people, potentially increasing to 400 million by 2025.[4] In
2010, overall asthma prevalence in the US was 8.4%.[3]
Healthcare data from the US show that there were 1.2 million hospital outpatient department visits and
479,300 hospitalisations for asthma in 2009.[3] Hospitalisation rates and asthma deaths were highest among
black people.[3] Despite the improved understanding of pathophysiology and treatment methods, asthma
continues to be undertreated.
Aetiology
Asthma is a complex disease with underlying multi-gene association interacting with environmental
exposure.[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]
The genes associated with the disease include, but are not limited to, ADAM 33,[6] [21] [22] [23] [24] [25]
[26] dipeptidyl peptidase 10,[27] [28] PHD finger protein 11,[27] [28] prostanoid DP1 receptor,[27] [28]
chromosome 12q,[29] and polymorphisms in tumour necrosis factor (TNF).[30] [31]
Patients' genetic make-up may predispose them to hyper-responsiveness to environmental aetiological

triggers. Those triggers include viral infections (e.g., rhinovirus, respiratory syncytial virus, human
metapneumovirus, and influenza virus), bacterial infections ( Mycoplasma pneumoniae or Chlamydia
pneumoniae ), allergen exposure (e.g., tree, grass, or weed pollen; fungi; or indoor allergens), occupational
exposures (e.g., animal or chemical), food additives and chemicals (e.g., metabisulfites), irritants, or aspirin
in predisposed people.[16]
Strong emotions and reactions, such as laughter, can also precipitate attacks[32] but often no clear aetiology
can be identified.
Pathophysiology
There are 2 major elements in the pathophysiology: inflammation and airway hyper-responsiveness (AHR).
The large airways and the small airways with diameters <2 micrometres are the sites of inflammation and
airway obstruction.[33] [34]
Airway inflammation occurs secondary to a complex interaction of inflammatory cells, mediators, and other
cells and tissues in the airway. An initial trigger leads to the release of inflammatory mediators, which leads
to the consequent activation and migration of other inflammatory cells. The inflammatory reaction is a T-
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jan 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Asthma in adults Basics
helper type 2 (Th2) lymphocytic response. Th2 inflammation is characterised by the presence of CD4+
lymphocytes that secrete interleukin (IL)-4, IL-5, and IL-13, the chemokine eotaxin, TNF-alpha,[35] and the
leukotriene LTB4, a product of the lipoxygenase pathway, as well as mast cell tryptase. This Th2 response is
important in the initiation and prolongation of the inflammatory cascade.
BASICS
Other WBCs involved are eosinophils, basophils and mast cells, macrophages, and invariant NK T cells,[36]
and in near-fatal or status asthmaticus, neutrophils are important.[17] These cells move to the airway,
causing changes in the epithelium, airway tone, and related autonomic neural control and hyper-secretion of
mucus, mucociliary function alteration and increased smooth muscle responsiveness. Pathological studies of
fatal asthma show severe hyper-inflation and mucous plugging with the mucus-containing mucins (proteins
that are present in the blood).[17] Tissue biopsies show the deposition of eosinophil granular proteins
throughout the lung tissue and damage of the epithelium mediated by those proteins. Denudation of the
basal layer by epithelial cell sloughing produces clumps of cells in the sputum referred to as Creola bodies.
There is also sub-basement membrane deposition of collagen often referred to as thickened basement
membrane, which is considered another hallmark.
Products of the inflammatory response induce smooth muscle contraction and consequent AHR. There
appear to be at least 2 different kinds of AHR: a baseline fixed and an episodic variable element.[37] The
underlying fixed AHR is possibly related to airway remodelling, whereas the variable AHR reflects the
action of the inflammatory mediators, and they are distinguished by direct and indirect bronchial challenges,
respectively. Finally, airway smooth muscle in asthmatic people is increased in mass, probably as a result of
hypertrophy and hyperplasia, which in vitro studies display as having increased contractility.[37]
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jan 29, 2018.
5
Asthma in adults Prevention
Secondary prevention
All patients with a history of near-fatal asthma, past intubation, or frequent intubations should use either
inhaled or nebulised short-acting beta agonists (SABA) on their way to the emergency department.
Patients with known allergic asthma should avoid precipitants.
All smokers should be encouraged to quit, and overweight patients should be encouraged to lose weight.
For patients with exercise-induced bronchospasm, a SABA used shortly before exercise (or as close to
exercise as possible) may be helpful for 2 to 3 hours. Long-acting beta agonists (LABA) can be protective
for up to 12 hours. When LABAs are administered on a daily basis, however, there is some shortening of the
duration of protection, even in patients using inhaled corticosteroids. Frequent and chronic use of LABAs for
exercise-induced bronchospasm should be discouraged. Such use may disguise poorly controlled persistent
asthma.[1] [99] LABA monotherapy should not be given in asthma due to the risk of serious asthma-related
events (asthma-related death, intubation, and hospitalisation). There is some evidence to suggest that fish oil
supplementation may be beneficial in exercise-induced bronchoconstriction, but not in regular management
of asthma.[100]
PREVENTION
Annual influenza vaccination is recommended for people with severe persistent asthma (including those who
require frequent hospitalisation). Despite previous concerns that influenza vaccine might precipitate asthma
attacks, current evidence suggests that there is a very low risk of an asthma attack. Although recommended
in guidelines, influenza vaccination has not been shown to protect against asthma exacerbations.
Asthma in adults Diagnosis
Case history
Case history #1
A 25-year-old woman presents with shortness of breath. She reported that in high school, she
occasionally had shortness of breath and would wheeze after running. She experiences the same
symptoms when she visits her friend who has a cat. Her symptoms have progressively worsened over the
past year and are now a constant occurrence. She also finds herself wheezing when waking from sleep
approximately twice a week.
Other presentations
Asthma commonly presents in children, but may present in otherwise healthy middle-aged individuals.
Symptoms may start as a non-productive cough, chest tightness, shortness of breath, or wheezing, either
spontaneously or on exposure to trigger factors. When the cough is productive, it is associated with clear
and sometimes stringy sputum. Frequently, the patient is a non-smoker and will often have an atopic
history, such as childhood eczema. In people with nasal polyps, examination of the lung is usually normal.
Exercise-induced symptoms may occur in around 50% to 65% of people with asthma. The concept of the
'cough-variant asthma' syndrome was popularised in the mid-1980s and it has become an all-embracing
label for the symptom of recurrent cough. This has resulted in overdiagnosis of asthma and inappropriate
therapy. 'Cough-variant’ asthma is rare and its existence is now questioned.
Step-by-step diagnostic approach

Diagnosis involves identification of typical signs and symptoms, and confirmatory tests.
History
DIAGNOSIS
Recurrent episodes of dyspnoea, chest tightness, wheezing, or coughing typically occur.
The patient's medical history may help to identify allergen exposures that worsen the asthma: for
example, episodes may be exacerbated by exposure to irritants such as tobacco smoke or fumes from
chemicals, such as bleach. Attacks may occur seasonally or upon exposure to cats in allergic patients.
Exercise can also make the symptoms worse.
More severely asthmatic people have night-time symptoms, waking them up from sleep. In severe
exacerbations, patients are continuously short of breath and may use accessory muscles of respiration.
Physical examination
The examination may be normal in patients with bronchial asthma. Examination of the nasal passages
may reveal nasal polyposis or nasal congestion. Chest auscultation may reveal expiratory wheezes.
With more severe asthma, the wheezes may be audible without the use of a stethoscope. In patients with
severe exacerbations, the lung examination may be silent.
7
Tests
For patients presenting for the first time, CXR, FBC, and differential are indicated in the initial work-up,
to exclude other pathologies. For patients presenting with an acute exacerbation, these may also be
performed if complicating factors are suspected from history and exam.
Pulmonary function testing (PFT), including forced expiratory volume at 1 second (FEV1), forced vital
capacity (FVC), and FEV1/FVC ratio showing airflow obstruction, can help diagnose asthma. The
diagnosis of asthma is confirmed by demonstrating reversibility of airflow obstruction (usually defined as
improvement in FEV1 by 12% and 200 mL) to short-acting bronchodilator; however, it should be noted
that a normal PFT result is possible during periods of quiescence.
Peak expiratory flow rate (PEFR) monitoring demonstrating diurnal variability (defined as [highest daily
PEFR - lowest daily PEFR]/[highest daily PEFR]) can help diagnose asthma, especially occupational
(work-related) asthma. The diagnosis of asthma is supported if PEFR varies by at least 20% for 3 days in
a week over several weeks or PEFR increases by at least 20% in response to asthma treatment. It is also
useful as an alternative to spirometry in an acute setting and can be readily performed as an outpatient or
in the home to monitor disease progress for monitoring progress. However, PEFR does not always reflect
the level of obstruction of the lung as accurately as the FEV1 and FEV1/FVC ratio, and accuracy depends
on the patient's effort.
Allergy testing is indicated in patients with a possible allergic component to their disease, including skin-
prick testing and immunoassay for allergen-specific IgE (replacing the radioallergosorbent test [RAST]).
These tests can reliably determine sensitivity to inhalant allergens to which the patient is exposed. Allergy
testing is recommended for patients with persistent asthma requiring regular preventer therapy. It may
also be considered in patients with asthma and allergic rhinitis to clarify whether allergens are contributing
to disease. If allergy is not present there is no need to consider anti-allergy measures.
Challenge tests to diagnose asthma are divided into: direct (using agents that directly constrict airway
smooth muscle (i.e., histamine or methacholine) and indirect (methods or agents that activate mast
cells to release mediators such as histamine and leukotrienes to constrict airway smooth muscle: e.g.,
DIAGNOSIS
exercise, eucapnic hyperventilation, inhaled hypertonic saline, mannitol, or adenosine monophosphate)

challenges. These direct and indirect challenges reflect the baseline fixed (airway remodelling) and
episodic variable (inflammatory) components of airway hyper-responsiveness, respectively.[42] They may
be considered if spirometry and PEFR do not show reversibility and variability.
Exhaled nitric oxide levels can be used to monitor a patient over time and, in combination with sputum
eosinophilia, has a high sensitivity and specificity; however, neither is a standard test in the UK or US at
present.[43] [44] [45]
[VIDEO: Peak flow measurement animated demonstration ]
Risk factors
Strong
FHx
• A parental history of asthma is a major risk factor for early development of asthma.[1]
• Multiple genes are implicated that predispose people to hyper-responsiveness to environmental
aetiological triggers.
allergens
• Common allergens include cats; dogs; cockroaches; dust mites; fungal spores; tobacco smoke; fumes
from chemicals, such as bleach; and pollen from trees, weeds, and grass.
• Workers commonly affected by occupational allergens include bakers, farmers, carpenters, and people
involved in manufacturing plastics, foams, and glues.
atopic history
• History of eczema, atopic dermatitis, allergic rhinitis is strongly associated.
Weak
nasal polyposis
• Inflammatory syndrome of nasal polyposis, aspirin intolerance, and asthma.[38]
• Nasal polyps are associated with late-onset versus childhood asthma.
obesity
• Increasing rates of obesity appear to parallel increasing rates of asthma prevalence, but the cause of
the correlation is uncertain.[1]
• Postulated mechanisms include reduced lung and tidal volume (promoting airway narrowing), low-
grade systemic inflammation, effect of comorbidities, or a common aetiology.[39] [40]
gastro-oesophageal reflux
• Prevalent in patients with poorly controlled asthma. However, treatment with a proton-pump inhibitor
does not improve asthma control.[41]
History & examination factors
DIAGNOSIS
Key diagnostic factors
presence of risk factors (common)
• Key risk factors include a FHx of asthma, exposure to allergens (e.g., dust mites, pets, tobacco
smoke), or history of atopic diseases (e.g., eczema, allergic rhinitis).
recent upper respiratory tract infection (common)

• With a recent sinusitis or common cold, symptoms are typically exacerbated.
dyspnoea (common)
• Precipitated by allergen exposure, exposure to cold air, tobacco smoke, or particulates; worse with
emotions such as laughing hard.
• May wake patient from sleep.
cough (common)
9
• May wake patient from sleep.
expiratory wheezes (common)

• Polyphonic, high-pitched expiratory wheezes are typical of asthma.
nasal polyposis (common)

• Appear as single or multiple polyps in the nasal cavity.
Diagnostic tests
1st test to order
Test Result
FEV1/FVC ratio FEV1/FVC <80% of
predicted
• Forced expiratory volume at 1 second (FEV1)/forced vital capacity
(FVC) ratio is the primary diagnostic test.
• If normal results and signs and symptoms are consistent with
diagnosis, then should undergo pulmonary function tests (PFTs)
before and after a methacholine challenge.
• FEV1 after bronchodilator should show at least 200 mL and 12%
improvement.
• FEV1/FVC ratio may be repeated annually.
• Moderate sensitivity and high specificity.
FEV1 FEV1 <80% of predicted
• A 20% drop in the FEV1 is diagnostic.
• If normal results and signs and symptoms are consistent with
diagnosis, should undergo PFTs before and after a methacholine
challenge.
DIAGNOSIS
• FEV1 may be used for subsequent follow-up at least once a year.
Test Result
peak expiratory flow rate (PEFR) flow rate as a comparison
to patient's personal
• If peak flow monitoring is performed, the written asthma action plan
best or normal values for
should use the patient's personal best peak flow as the reference
height and gender
value.
• Long-term daily PEFR monitoring should be considered for: patients
who have moderate or severe persistent asthma; patients who have
a history of severe exacerbations; patients who poorly perceive
airflow obstruction and worsening asthma; or patients who prefer this
monitoring method.
• Long-term daily PEFR monitoring can be helpful to: detect early
changes in disease states that require treatment; evaluate responses
to changes in therapy; and afford a quantitative measure of
impairment.
• PEFR flow monitoring during exacerbations will help determine the
severity of the exacerbations and guide therapeutic decisions in the
home, school, clinicians' surgery, or emergency department.[1]
[VIDEO: Peak flow measurement animated

demonstration ]
CXR normal or hyper-inflated
• Indicated in first presentation to exclude other pathologies, and in
acute exacerbations when complicating factors are suspected from
history and examination.
• May also show signs of infection in acute exacerbation or
pneumothorax.
FBC normal or raised
eosinophils and/or
• Indicated in first presentation and in acute exacerbations when
neutrophilia
complicating factors are suspected from history and examination.
Other tests to consider
DIAGNOSIS
Test Result
bronchial challenge test positive
• May be considered if spirometry and PEFR do not show reversibility
and variability.
• Challenge tests to diagnose asthma are divided into: direct (using
agents that directly constrict airway smooth muscle (i.e., histamine
or methacholine) and indirect (methods or agents that activate
mast cells to release mediators such as histamine and leukotrienes
to constrict airway smooth muscle: e.g., exercise, eucapnic
hyperventilation, inhaled hypertonic saline, mannitol, or adenosine
monophosphate) challenges. These direct and indirect challenges
reflect the baseline fixed (airway remodelling) and episodic variable
(inflammatory) components of airway hyper-responsiveness,
respectively.[42]
immunoassay for allergen-specific IgE positive for allergen
• Useful in allergic asthma for identifying allergen and directing
immunotherapy.
11
Test Result
skin prick allergy testing positive for allergen
• Useful in allergic asthma for identifying allergen and directing
immunotherapy.
• Allergy testing is recommended for patients with persistent asthma
requiring regular preventer therapy. It may also be considered in
patients with asthma and allergic rhinitis to clarify whether allergens
are contributing to disease. If allergy is not present there is no need
to consider anti-allergy measures.
Emerging tests
Test Result
exhaled nitric oxide (eNO) increased
• Results are variable between machines and people.
• Most useful in following patient over time and monitoring adherence
to treatment.
• In combination with sputum eosinophilia, has a high sensitivity and
specificity.[43] [44] [45]
• Not a standard test in the UK or US at present.
sputum eosinophilia increased
• Increased with T-helper type 2 inflammation.
• Reflects the level of inflammation in the airway and the response to
inhaled corticosteroid.
• Limited by patient's ability to produce sputum after induction.
• A combination of eNO and sputum eosinophilia has a high specificity
and sensitivity.
• Repeat test in follow-up.
• Not commonly done.
Differential diagnosis
DIAGNOSIS
Condition Differentiating signs / Differentiating tests

symptoms
Cystic fibrosis • Chronic, sometimes • Sweat chloride testing: level
productive cough with a of sweat chloride ≥60 mEq/L.
possible family history of CF. • Consider repeat testing.
• Nasal polyposis at or
before 12 years of age and
symptoms related to other
organ involvement, such as
diarrhoea, malabsorption, or
failure to thrive.

symptoms
Chronic rhinosinusitis • May present with nocturnal • Anterior rhinoscopy or
cough and dyspnoea from nasal endoscopy may show
post-nasal discharge. inflammation, purulent
• May co-exist with asthma. discharge, oedema, or frank
polyps.
• CT may show opacification
of involved sinuses, mucosal
thickening, air-fluid levels, or
anatomical abnormalities.
Tracheomalacia • Symptoms are usually • The sensitivity of plain

positionally dependent and x-rays is 62%, using
occur within the first weeks microlaryngoscopy and
or months of life. bronchoscopy as the
• Expiratory stridor and a reference standards.
barking brassy cough, • In addition to CXR, barium
and wheezing respiratory oesophagography is useful
distress with additional for evaluating associated
breath sound at the end disease processes, such as
of expiration (the bagpipe tracheo-oesophageal fistula
sign), are accompanied by and reflux disease.
the occasional extension
of the neck with breathing,
inspiratory stridor, episodes
of holding of breath, anoxia,
recurrent respiratory
infections, retraction of
intercostal and subcostal
muscles, failure to thrive,
and respiratory and cardiac
arrest.[49]
Vascular ring • Wheezing, shortness of • CT chest with contrast:
DIAGNOSIS
breath, occasional stridor. double aortic arch, abnormal
take-off of the innominate
artery, anomaly of left
pulmonary artery, right
aortic arch, aberrant right
subclavian, enlarged
pulmonary veins.[49]
Foreign body aspiration • Wheezing, shortness of • CXR, CT chest, or

breath, occasional stridor are bronchoscopy shows the
common. foreign body.
• If the foreign body is in the
peripheral airway, localised
one-sided wheezing or
collapse of the distal lung
tissue is found.
13

symptoms
Vocal cord dysfunction • Inspiratory and expiratory • Direct visualisation of
wheezing is often difficult to the vocal cords with
differentiate. rhinolaryngoscopy during
• Should be considered in a spell. Inspiratory flow
steroid-resistant asthma volume loop is helpful when
patients, but may be co- abnormal (flattened).
existent with asthma.
Alpha-1 antitrypsin • Wheezing, resistant to • Testing for the alpha-1

deficiency management. antitrypsin phenotype.
• May have family history of
parents or grandparents
dying of lung disease.
COPD • History of smoking. • PFTs with residual volume

• Dyspnoea occurs with (RV), total lung capacity
or without wheezing and (TLC), and a flow volume
coughing. loop with bronchodilator
• Examination may show showing an obstructive
barrel chest, hyper- pattern with an increase in
resonance to percussion, TLC and RV and a reduction
and distant breath sounds. in forced expiratory flow at
one second (FEV1), FEV1/
forced vital capacity (FVC)
ratio <70%; total absence
of reversibility is neither
required nor the most typical
result.
• CXR showing hyper-inflation
of the lungs.
Bronchiectasis • Dyspnoea, cough, and • High-resolution CT chest:

wheezing and, if severe, dilated airways, bronchial
DIAGNOSIS
recurrent pulmonary wall thickening.

infections. • Can occasionally be seen on
CXR.
Pulmonary embolism • Patients have a wide variety • Risk stratification with

of presentations but most appropriate scoring systems
common is shortness of and serum D-dimer
breath and pleuritic pain. measurements should be
done.
• Confirmation of pulmonary
embolism can be done using
CT pulmonary angiography.
Alternative tests include the
less sensitive V/Q scan.

symptoms
Congestive heart failure • History of CAD or • CXR may show increased
uncontrolled HTN. alveolar markings, fluid
• Examination shows in fissures, and pleural
dependent oedema, elevated effusions.
jugular venous pressure, • Echocardiogram may show
and basal pulmonary reduced or preserved left
crepitations. ventricular ejection fraction.
Serum B-natriuretic peptide
may be elevated.
Common variable • History of recurrent, usually • Serum IgG level <5g/L (500
immunodeficiency sinopulmonary, infections. mg/dL).
Diagnostic criteria
Clinical classification of asthma (before treatment)[1]
Of note, the classification may change over time depending on the patient's health status. One factor in each
category is sufficient to classify patient. Asthma is a variable disease, thus there can be overlap between
categories.
Mild intermittent:
• Symptoms ≤2 times a week

• Asymptomatic and normal peak expiratory flow rate (PEFR) between attacks
• Attacks are brief with varying intensity
• Night-time symptoms ≤2 times a month
• Forced expiratory flow at 1 second (FEV1) or PEFR ≥80% of predicted
• PEFR variability <20%.
DIAGNOSIS
Mild persistent:
• Symptoms >2 times a week but <1 time a day

• Exacerbations may affect activity
• Night-time symptoms >2 times a month
• FEV1 ≥80% of predicted
• PEFR variability between 20% and 30%.
Moderate persistent:
• Daily symptoms
• Use of short-acting beta agonists daily
• Attacks affect activity
• Exacerbations ≥2 times a week and may last for days
• Night-time symptoms >1 time a week
• FEV1 greater than 60% to <80% of predicted
• PEFR variability >30%.
Severe persistent:
15
• Continual symptoms
• Limited physical activity
• Frequent exacerbations
• Frequent night-time symptoms
• FEV1 ≤60% of predicted
DIAGNOSIS
Asthma in adults Treatment
Step-by-step treatment approach

The main goal of treatment is to achieve maximum control of symptoms with the fewest medications.
Asthma control refers to the extent to which the manifestations of asthma have been reduced or removed
by treatment.[50] Optimal control should include assessment of a combination of the patient's symptoms
and the PFTs. The goal for optimal control is to have the patient asymptomatic with normal PFTs if possible.
Once a state of control is achieved, an attempt should be made to reduce the doses of medications while
maintaining optimal control and minimising any adverse effects.
Stepwise therapy for long-term management

Guidelines recommend that asthma severity and control be viewed as a ladder in which medication can
be stepped up or stepped down based on the severity of the disease and adequacy of the control: for
example, as determined by asthma control test.[1] [51] The stepwise approach is meant to assist, not
replace, the clinical decision making required to meet individual patient needs.
Patients may start at any step of the ladder, and medications can be added (stepped up) if needed.
Increasing use of a short-acting beta agonist (SABA) or use >2 days a week for symptom relief (not
prevention of exercise-induced bronchospasm) generally indicates inadequate control and the need to
step up treatment.
Regular assessment of patient's asthma control should be carried out with the aim of stepping down the
ladder if disease has been well controlled for at least 3 months.
Education and environmental control

All patients at all steps of therapy should receive adequate patient education and should take
environmental control measures.
Exercise-induced asthma
Exercise-induced symptoms may occur in around 50% to 65% of people with asthma. Inhaled
corticosteroids (ICS) have been shown to significantly reduce the severity of exercise-induced asthma.
Sodium cromoglicate, nedocromil sodium, or a bronchodilator can be used immediately before exercise
(or as rescue medication) until the full effect of ICS is realised. Other medications include long-acting
beta-agonists used in combination with ICS, which can be used successfully for prevention of exercise-
induced asthma in patients with abnormal spirometry and/or more persistent symptoms. Leukotriene
receptor antagonists are also used to control exercise-induced asthma and provide 50% to 60%
protection when given as tablets for up to 24 hours
Allergen immunotherapy
For well-controlled confirmed allergic asthma, treatment with allergen immunotherapy is an option. This
treatment is only used with documented allergies either by skin testing or specific IgE serology and should
only be given with adequate supervision to prevent adverse systemic allergic reactions.[52] [53]
TREATMENT
Step 1: mild intermit tent and exercise-induced asthma

Defined as:
• Symptoms ≤2 times a week
17
• Asymptomatic and normal peak expiratory flow rate (PEFR) between attacks
• Attacks are brief with varying intensity
• Night-time symptoms ≤2 times a month
• Forced expiratory flow at 1 second (FEV1) or PEFR ≥80% of predicted
• PEFR variability <20%.
For those patients with mild intermittent asthma or exercise-induced asthma, the use of a SABA on an 'as
required' basis is sufficient alone.1[B]Evidence
All patients should have access to quick-relief SABAs. Increasing use of a SABA or use >2 days a week
for symptom relief (not prevention of exercise-induced bronchospasm) generally indicates inadequate
control and the need to step up treatment.
Step 2: mild persistent

Defined as:
• Symptoms >2 times a week but <1 time a day

• Exacerbations may affect activity
• Night-time symptoms >2 times a month
• FEV1 ≥80% of predicted
• PEFR variability between 20% and 30%.
A low-dose inhaled corticosteroid (ICS) is added if control is not achieved with a SABA used on an 'as
needed' basis only.[54] 2[B]Evidence
Second-line options that can be used instead of a low-dose ICS are sodium cromoglicate or nedocromil, a
leukotriene-receptor antagonist (LTRA),[55] 3[B]Evidence or theophylline.
All patients should have access to quick-relief SABAs.
Step 3: moderate persistent

Defined as:
• Daily symptoms
• Use of short-acting beta agonists daily
• Attacks affect activity
• Exacerbations ≥2 times a week and may last for days
• Night-time symptoms >1 time a week
• FEV1 >60% to <80% of predicted
Adds a long-acting beta agonist (LABA) to a low-dose ICS,[56] [57] or increases the dose of the ICS to
a medium-dose range.4[B]Evidence LABA monotherapy should not be given in asthma due to the risk of
serious asthma-related events (asthma-related death, intubation, and hospitalisation).
Second-line alternatives to either increasing the ICS dose or adding an LABA are to combine a low-dose
TREATMENT
ICS with either an LTRA,[55] 5[B]Evidence theophylline,6[C]Evidence or zileuton.
Steps 4 to 6: severe persistent
Defined as:
• Continual symptoms
• Limited physical activity
• Frequent exacerbations
• Frequent night-time symptoms
• FEV1 ≤60% of predicted
Preferred combination treatment for step 4 is a medium-dose ICS plus a long-acting bronchodilator. A
long-acting bronchodilator can be substituted with either an LTRA, theophylline, or zileuton. Addition
of tiotropium to an ICS has been shown to improve symptoms and lung function in patients with
inadequately controlled asthma. Its effects appear to be equivalent to those seen with the addition of
salmeterol.[58] [59] [60] Addition of tiotropium may also decrease the risk of severe exacerbations.[61]
Step 5 changes a medium-dose ICS to a high-dose ICS. The US National Institutes of Health (NIH)
guidelines recommend high doses of ICS in adults with severe persistent asthma.[1] There are no
maximum doses for high-dose inhaled corticosteroid therapy reported in the guidelines. Therefore, the
dose should be increased gradually and cautiously according to patient response and adverse effects.
At these high doses, adrenal suppression is likely; therefore, specialist pulmonary assessment should
be sought before initiating this type of therapy. It should be noted that the manufacturer's recommended
maximum dose is lower than the doses suggested in the guidelines. An immunomodulator (i.e.,
omalizumab) can be considered in patients with allergies.[62] [63] [64] [65] Benralizumab, a monoclonal
antibody directed at the alpha chain of the interleukin-5 receptor, is licensed for the add-on treatment of
patients with severe asthma aged 12 years and older, who have an eosinophilic phenotype.[66] [67]
Step 6 adds oral corticosteroids to existing treatments.
Treatment details overview

Consult your local pharmaceutical database for comprehensive drug information including contraindications,
drug interactions, and alternative dosing. ( see Disclaimer )
Acute ( summary )
Patient group Tx line Treatment
step 1: mild intermit tent and 1st short-acting beta agonist (SABA) as
TREATMENT
exercise-induced asthma needed
step 2: mild persistent 1st low-dose inhaled corticosteroid (ICS)
19
Acute ( summary )
adjunct short-acting beta agonist (SABA) as
needed
2nd leukotriene-receptor antagonist (LTRA)

or sodium cromoglicate or nedocromil or
theophylline

needed
step 3: moderate persistent 1st low-dose inhaled corticosteroid (ICS)
plus long-acting beta agonist (LABA)

needed
step 3: moderate persistent 1st medium-dose inhaled corticosteroid (ICS)

needed
2nd low-dose inhaled corticosteroid (ICS) +

leukotriene-receptor antagonist (LTRA) or
theophylline or zileuton

needed
step 4: severe persistent 1st medium-dose inhaled corticosteroid (ICS)
plus long-acting beta agonist (LABA) or

tiotropium

needed
2nd medium-dose inhaled corticosteroid (ICS)

+ leukotriene-receptor antagonist (LTRA)
or theophylline or zileuton

needed
step 5: severe persistent, 1st high-dose inhaled corticosteroid (ICS)

inadequate response to medium-
dose inhaled corticosteroids (ICS)
TREATMENT
+ adjunctive medications

tiotropium
adjunct immunomodulator
Acute ( summary )
needed
step 6: severe persistent, 1st oral corticosteroid

inadequate response to high-dose
inhaled corticosteroids (ICS) +
adjunctive medications
plus high-dose inhaled corticosteroid (ICS)

tiotropium

needed
Ongoing ( summary )
all patients 1st patient education and environmental

control
known single allergen adjunct allergen immunotherapy
TREATMENT
21
Treatment options
Acute
step 1: mild intermit tent and 1st short-acting beta agonist (SABA) as
exercise-induced asthma needed
» Mild intermittent is defined as: symptoms ≤2
times a week; asymptomatic and normal peak
expiratory flow rate (PEFR) between attacks;
attacks are brief with varying intensity; night-time
symptoms ≤2 times a month; forced expiratory
flow at 1 second (FEV1) or PEFR ≥80% of
predicted; PEFR variability <20%.
[VIDEO: Peak flow measurement

animated demonstration ]
» The use of a SABA on an 'as required' basis is
sufficient alone.1[B]Evidence
» Increasing use of a SABA or use >2 days

a week for symptom relief (not prevention of
exercise-induced bronchospasm) generally
indicates inadequate control and the need to
step up treatment.
Primary options
» salbutamol inhaled: (100 micrograms/dose

metered-dose inhaler) 100-200 micrograms
(1-2 puffs) up to four times daily when
required if shortness of breath or 5 minutes
prior to exercise
OR
Primary options
» levosalbutamol inhaled: (45 micrograms/

dose metered-dose inhaler) 45-90
micrograms (1-2 puffs) every 4-6 hours
when required if shortness of breath or 5-30
minutes prior to exercise
step 2: mild persistent 1st low-dose inhaled corticosteroid (ICS)

» Mild persistent is defined as: symptoms >2
TREATMENT
times a week but <1 time a day; exacerbations

may affect activity; night-time symptoms >2
times a month; FEV1 ≥80% of predicted; peak
expiratory flow rate (PEFR) variability between
20% and 30%.
Acute
» A low-dose ICS is added if control is not
achieved with a short-acting beta agonist used
on an 'as needed' basis only.[68] 2[B]Evidence
» ICS are given in divided doses, generally using

a spacer/holding chamber device if using a
metered-dose inhaler.[69]
Primary options
» fluticasone propionate inhaled: (50, 125,

250 micrograms/dose metered dose inhaler)
100-300 micrograms/day
OR
Primary options
» budesonide inhaled: (90, 180, or 200

micrograms/dose breath-actuated inhaler)
OR
Primary options
» flunisolide inhaled: (80 micrograms/dose

metered-dose inhaler) 320 micrograms/day
OR
Primary options
» beclometasone inhaled: (50, 100, or 200

micrograms/dose metered-dose inhaler)
OR
Primary options
» mometasone inhaled: (200 micrograms/

dose breath-actuated inhaler) 200
micrograms/day
OR
Primary options
» ciclesonide inhaled: (80 or 160 micrograms/

micrograms/day
TREATMENT

needed
23
Acute
step up treatment.
Primary options

prior to exercise
OR
Primary options

2nd leukotriene-receptor antagonist (LTRA)
or sodium cromoglicate or nedocromil or
theophylline
» These therapies are considered potential
second-line alternatives to inhaled
corticosteroids (ICS).
» Sodium cromoglicate and nedocromil have

some, but limited, effectiveness, and a strong
safety profile. A 4- to 6-week trial may be needed
to determine maximal benefit; once control is
achieved, dose may be reduced.
» LTRAs, such as montelukast and zafirlukast,

provide long-term control, prevent symptoms,
and are alternative, but not preferred, therapies
for patients who have mild persistent asthma,
because studies comparing overall efficacy of
ICS and LTRAs favour ICS on most asthma
outcome measures. They should not be used for
acute attacks or as monotherapy for exercise-
induced bronchospasm.[70] [71]
» Sustained-release theophylline is an
alternative, but not preferred, long-term control
medication. It is not preferred because the
modest clinical effectiveness (theophylline
is primarily a bronchodilator and its anti-
inflammatory activity demonstrated thus far is
TREATMENT
modest) must be balanced against concerns

about potential toxicity.[72] Theophylline remains
a therapeutic option for certain patients due to
expense or need for tablet-form medication.
Serum monitoring is important due to wide inter-
patient variation. Sustained-release theophylline
Acute
is given to achieve a serum concentration of
between 5 and 15 micrograms/mL at steady
state. Periodic theophylline monitoring is
necessary to maintain a therapeutic, but not
toxic, level.
Primary options
» montelukast: 10 mg orally once daily in the

evening
OR
Primary options
» zafirlukast: 20 mg orally twice daily
OR
Primary options
» theophylline: 10 mg/kg/day (maximum 300

mg/day) orally (immediate-release) initially
given in divided doses every 6-8 hours,
increase gradually according to response and
serum drug level, maximum 400-1600 mg/day
Extended-/controlled-release formulations are
available.
OR
Primary options
» sodium cromoglicate inhaled: (20 mg

spincaps) 20 mg four times daily
OR
Primary options
» nedocromil inhaled: (2 mg/dose metered-

dose inhaler) 4 mg (2 puffs) four times daily
needed
step up treatment.
Primary options
TREATMENT

prior to exercise
25
Acute
OR
Primary options

step 3: moderate persistent 1st low-dose inhaled corticosteroid (ICS)

» Moderate persistent is defined as: daily
symptoms; use of short-acting beta agonists
daily; attacks affect activity; exacerbations ≥2
times a week and may last for days; night-time
symptoms >1 time a week; FEV1 >60% to <80%
of predicted; peak expiratory flow rate (PEFR)
variability >30%.

Primary options

OR
Primary options

OR
Primary options

OR
Primary options

TREATMENT
OR
Primary options
Acute
micrograms/day
OR
Primary options

micrograms/day
plus long-acting beta agonist (LABA)
» Step 3 therapy adds an LABA.[56] [57]
» LABA monotherapy should not be given in

asthma due to the risk of serious asthma-related
events (asthma-related death, intubation, and
hospitalisation).
Primary options
» salmeterol inhaled: (50 micrograms/dose

dry powder inhaler) 50 micrograms (1 puff)
twice daily
OR
Primary options
» formoterol inhaled: (12 micrograms/dose

every 12 hours
needed
step up treatment.
Primary options

prior to exercise
OR
TREATMENT
Primary options

27
Acute
step 3: moderate persistent 1st medium-dose inhaled corticosteroid (ICS)

» Moderate persistent is defined as: daily
symptoms; use of short-acting beta agonists
daily; attacks affect activity; exacerbations ≥2
times a week and may last for days; night-time
symptoms >1 time a week; FEV1 >60% to <80%
of predicted; peak expiratory flow rate (PEFR)
variability >30%.
» Step 3 therapy may involve increasing the

dose of the ICS to a medium-dose range
rather than adding a long-acting beta-agonist
(LABA).4[B]Evidence

Primary options

OR
Primary options
» budesonide inhaled: (200 micrograms/

dose breath-actuated inhaler) 600-1200
micrograms/day
OR
Primary options

metered-dose inhaler) 320-640 micrograms/
day
OR
Primary options

TREATMENT
OR
Primary options
Acute
micrograms/day
OR
Primary options

micrograms/day
needed
step up treatment.
Primary options

prior to exercise
OR
Primary options

2nd low-dose inhaled corticosteroid (ICS) +
leukotriene-receptor antagonist (LTRA) or
theophylline or zileuton
» Second-line alternative is to combine a low-
dose ICS with either an LTRA,[55] 5[B]Evidence
theophylline,6[C]Evidence or zileuton.

TREATMENT

29
Acute
between 5 and 15 micrograms/mL. Periodic
theophylline monitoring is necessary to maintain
a therapeutic, but not toxic, level.[73]
Primary options

-or-
-or-
-or-
-or-
micrograms/day
-or-
micrograms/day
--AND--
evening
-or-
-or-
available.
-or-
» zileuton: 600 mg orally four times daily
TREATMENT

needed
Acute
step up treatment.
Primary options

prior to exercise
OR
Primary options

step 4: severe persistent 1st medium-dose inhaled corticosteroid (ICS)

» Severe persistent is defined as: continual
symptoms; limited physical activity; frequent
exacerbations; frequent night-time symptoms;
FEV1 ≤60% of predicted; peak expiratory flow
rate (PEFR) variability >60%.

Primary options

OR
Primary options

micrograms/day
OR
Primary options
TREATMENT

day
OR
31
Acute
Primary options

OR
Primary options

micrograms/day
OR
Primary options

micrograms/day
tiotropium
» Preferred treatment is to add an LABA
to a medium-dose inhaled corticosteroid
(ICS).7[B]Evidence 4[B]Evidence

hospitalisation).
» Addition of tiotropium to an ICS has been

shown to improve symptoms and lung function
in patients with inadequately controlled asthma.
Its effects appear to be equivalent to those seen
with the addition of salmeterol.[58] [59] [60]
Primary options

twice daily
OR
Primary options

TREATMENT
every 12 hours
OR
Primary options
Acute
» tiotropium inhaled: (1.25 micrograms/
dose inhalation solution) 2.5 micrograms
(2 inhalations) once daily; (18 micrograms/
dose inhalation powder) 18 micrograms (1
inhalation) once daily
needed
step up treatment.
Primary options

prior to exercise
OR
Primary options

2nd medium-dose inhaled corticosteroid (ICS)
+ leukotriene-receptor antagonist (LTRA)
or theophylline or zileuton
» Second-line alternative is to combine a
medium-dose ICS with either an LTRA,[55]
5[B]Evidence theophylline,6[C]Evidence or
zileuton.

TREATMENT

33
Acute
between 5 and 15 micrograms/mL. Periodic
theophylline monitoring is necessary to maintain
a therapeutic, but not toxic, level.
Primary options

-or-
micrograms/day
-or-
day
-or-
-or-
micrograms/day
-or-
micrograms/day
--AND--
evening
-or-
-or-
available.
-or-
» zileuton: 600 mg orally four times daily
needed
TREATMENT

step up treatment.
Acute
Primary options

prior to exercise
OR
Primary options

step 5: severe persistent, 1st high-dose inhaled corticosteroid (ICS)

inadequate response to medium-
dose inhaled corticosteroids (ICS)
+ adjunctive medications
» The US National Institutes of Health (NIH)

guidelines recommend high doses of ICS in
adults with severe persistent asthma.[1] There
are no maximum doses for high-dose inhaled
corticosteroid therapy reported in the guidelines.
Therefore, the dose should be increased
gradually and cautiously according to patient
response and adverse effects. At these high
doses, adrenal suppression is likely; therefore,
specialist pulmonary assessment should be
sought before initiating this type of therapy.
It should be noted that the manufacturer's
recommended maximum dose is lower than the
doses suggested in the guidelines.

» Fluticasone has been reported to suppress

the pituitary-adrenal axis at high doses (800
micrograms/day) in single case reports.[74] [75]
TREATMENT
Primary options

consult specialist for guidance on dose;
35
Acute
doses >500 micrograms/day are generally
required
OR
Primary options
» budesonide inhaled: (200 micrograms/dose

breath-actuated inhaler) consult specialist for
guidance on dose; doses >1200 micrograms/
day are generally required
OR
Primary options

metered dose inhaler) consult specialist for
OR
Primary options
» beclometasone inhaled: (200, or 250

required
OR
Primary options

dose breath-actuated inhaler) consult
specialist for guidance on dose; doses >400
micrograms/day are generally required
OR
Primary options

dose metered-dose inhaler) consult
tiotropium
» Preferred treatment is to add an LABA to a
TREATMENT
high-dose ICS.7[B]Evidence 4[B]Evidence

hospitalisation).
Acute
Primary options

twice daily
OR
Primary options

every 12 hours
OR
Primary options

» Consider omalizumab for patients with known
allergy.[62] [63] [64] [76]
» Consider benralizumab for patients with an

eosinophilic subtype.[66] [67]
Primary options
» omalizumab: dose is dependent on body

weight and pretreatment IgE level
OR
Primary options
» benralizumab: 30 mg subcutaneously once

every 4 weeks for the first 3 doses, followed
by 30 mg once every 8 weeks thereafter
needed
TREATMENT

step up treatment.
37
Acute
Primary options

prior to exercise
OR
Primary options

step 6: severe persistent, 1st oral corticosteroid

inadequate response to high-dose
inhaled corticosteroids (ICS) +
adjunctive medications
» Step 6 adds oral corticosteroids to existing

treatments.
» Depending on the severity, taper the

corticosteroid dose every 3 to 5 days until the
course is complete. The more severe the attack,
the longer the treatment duration. Re-evaluate at
end of course.
Primary options
» prednisolone: 0.5 mg/kg/day orally given in

1-2 divided doses for 3-5 days
plus high-dose inhaled corticosteroid (ICS)
» The US National Institutes of Health (NIH)
guidelines recommend high doses of ICS in
adults with severe persistent asthma.[1] There
are no maximum doses for high-dose inhaled
corticosteroid therapy reported in the guidelines.
Therefore, the dose should be increased
gradually and cautiously according to patient
response and adverse effects. At these high
TREATMENT
doses, adrenal suppression is likely; therefore,

specialist pulmonary assessment should be
sought before initiating this type of therapy.
It should be noted that the manufacturer's
recommended maximum dose is lower than the
doses suggested in the guidelines.
Acute
» Fluticasone has been reported to suppress

the pituitary-adrenal axis at high doses (800
micrograms/day) in single case reports.[74] [75]
Primary options

required
OR
Primary options
» budesonide inhaled: (200 micrograms/dose

breath-actuated inhaler) consult specialist for
OR
Primary options

metered dose inhaler) consult specialist for
OR
Primary options
» beclometasone inhaled: (200, or 250

required
OR
Primary options

dose breath-actuated inhaler) consult
TREATMENT
OR
Primary options
39
Acute
dose metered-dose inhaler) consult
tiotropium
» Preferred treatment is to add an LABA to a
high-dose inhaled corticosteroid (ICS) and oral
corticosteroid.

hospitalisation).

Primary options

twice daily
OR
Primary options

every 12 hours
OR
Primary options

» Consider omalizumab for patients with known
allergy.[62] [63] [64] [76]
» Consider benralizumab for patients with an

TREATMENT
eosinophilic subtype.[66] [67]
Primary options
» omalizumab: dose is dependent on body

weight and pretreatment IgE level
Acute
OR
Primary options
» benralizumab: 30 mg subcutaneously once

every 4 weeks for the first 3 doses, followed
by 30 mg once every 8 weeks thereafter
needed
step up treatment.
Primary options

prior to exercise
OR
Primary options

Ongoing
all patients 1st patient education and environmental

control
» Environmental control strategies include
identifying and eliminating home and work/
school exposure (indoor or outdoor) to allergens
that can cause or worsen asthma, including
house-dust mites, animals, cigarette smoke and
other respiratory irritants, chemicals, and pollens
and grasses.
TREATMENT
» Occupational exposure should also be

assessed. Foods to which the patient is sensitive
should be identified and avoided (e.g., foods
containing sulfites).
41
Ongoing
» Patients should be counselled about avoiding
specific drugs (e.g., aspirin and non-steroidal
anti-inflammatory drugs, beta-blockers) where
necessary, immunisation (e.g., influenza),
smoking cessation (if applicable), treatment of
comorbidities (e.g., gastro-oesophageal reflux,
obesity, infections), correct use of medications
and delivery devices, self-monitoring of symptom
control, and the importance of an asthma action
plan.
[VIDEO: Peak flow measurement

animated demonstration ]
known single allergen adjunct allergen immunotherapy

» For well-controlled confirmed allergic asthma,
treatment with allergen immunotherapy is an
option.
» This treatment is only used with documented

allergies either by skin testing or specific IgE
serology and should only be given with adequate
supervision to prevent adverse systemic allergic
reactions.[52] [53]
TREATMENT
Emerging
Dupilumab
Dupilumab is a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor. In patients
with persistent moderate-to-severe asthma and elevated eosinophil levels, who used inhaled glucocorticoids
and long-acting beta agonists (LABAs), dupilumab therapy, compared with placebo, was associated with
fewer asthma exacerbations when LABAs and inhaled glucocorticoids were withdrawn, and with improved
lung function and reduced levels of Th2-associated inflammatory markers.[77]
Tralokinumab
Tralokinumab is a human IL-13-neutralising immunoglobulin G4 monoclonal antibody. In a placebo-
controlled phase II trial of adults with moderate to severe uncontrolled asthma despite controller therapies,
tralokinumab was associated with improved lung function at 13 weeks, but not asthma control assessed by
questionnaire.[78]
Mepolizumab
IL-5 is part of the T-helper type 2 (Th2) immune response, and modulating it will probably reduce the
inflammation in asthma and target airway remodelling. Phase III studies of anti-IL-5 (mepolizumab) have
shown a role in reducing exacerbations and oral corticosteroid dose in refractory eosinophilic asthma.[79]
[80] [81] [82] [83]
Reslizumab
Reslizumab is a humanised monoclonal antibody that binds to IL-5. It has been approved by the US
Food and Drug Administration (FDA) as add-on maintenance therapy in adults with severe asthma and
eosinophilic phenotype.
Lebrikizumab
Interleukin-13 (IL-13) is found in the airways of patients with asthma and is thought to mediate several
features of asthma, including airway hyper-responsiveness, inflammation, mucous metaplasia, and activation
and proliferation of airway fibroblasts, which contribute to adverse airway remodelling. In a clinical trial of
symptomatic moderate asthma despite taking inhaled corticosteroids and long-acting beta-agonists (LABAs),
there was an effect on airflow obstruction in all patients with the anti-IL13 antibody lebrikizumab. However,
the effect was greater in patients who had circulating levels of the Th2 marker protein periostin than in those
without this phenotype.[84]
Bronchial thermoplasty
Bronchial thermoplasty is a bronchoscopic procedure in which controlled thermal energy is applied to the
airway wall to decrease smooth muscle. In people with severe asthma, this procedure improves asthma-
specific quality of life with a reduction in severe exacerbations and healthcare use in the post-treatment
period. However, this is only available in limited specialised treatment centres.[85] [86] [87] [88]
TREATMENT
43
Asthma in adults Follow up
Recommendations
Monitoring
FOLLOW UP
Patients are recommended to self-monitor at home on a daily basis by checking and recording the peak
expiratory flow rate (PEFR) using a PEFR meter. PEFR results should help the patient adjust medication
use as instructed by the doctor, using an asthma action plan. PEFR monitoring becomes life-saving
for the group of patients who are unable to sense worsening of their asthma. PEFR is not, however, as
accurate a measure of pulmonary obstruction as is the forced expiratory volume at 1 second (FEV1)
and the FEV1/forced vital capacity (FVC) ratio. The frequency of the testing depends on the severity
of the patient's symptoms. In mildly symptomatic, well-controlled asthma, the test could be completed
once every 1 to 2 years. In more severe asthma, testing should be done more frequently to determine
medication compliance and the patient's ability to monitor and control symptoms.
Patient instructions
It is essential to inform the patient that effective home management of symptoms greatly improves
outcome. Self-monitoring on a daily basis should be encouraged by, for example, checking and recording
peak expiratory flow using the PEFR meter. When the patient discusses these results with his or her
physician, subsequent adjustment of medications can be made. It should be emphasised that attending
follow-up is essential for a long and healthy life with asthma.
Complications
Complications Timeframe Likelihood

severe exacerbation short term medium
May occur in poorly controlled disease or if exposed to a major trigger (e.g., alternaria-allergic asthmatic
people exposed to a high level of the allergen in a grain silo).
Other patients at risk include those with a history of previous near-fatal asthma attacks and those with
multiple hospitalisations. Patients on long-acting beta agonist (LABA) without a corticosteroid, and those
with a psychiatric disorder and history of medication non-compliance, are at high risk of severe asthma
attacks and death.[94]
Patient should be placed on oxygen, a continuous nebulised short-acting beta agonist (SABA) such
as salbutamol or levosalbutamol (with or without ipratropium), hydration, an inhaled corticosteroid, IV
magnesium,8[C]Evidence and, if deemed necessary, a methylxanthine (oral or IV) and/or adrenaline (IM),
with or without bilevel positive airway pressure or intubation and mechanical ventilation.[95]
Severe exacerbations are associated with a more rapid decline in lung function, but this decline is reduced
with inhaled corticosteroids.[96]
moderate exacerbation short term medium
Complications Timeframe Likelihood

Can occur in any asthmatic after an upper airway infection or a persistent allergen exposure.
FOLLOW UP
Counsel the patient on allergen removal and treat any upper or lower airway infection as necessary.
Exacerbation can be treated in the outpatient setting with an oral corticosteroid, and use of a short-acting
beta agonist on an as-needed basis.
Patients should be instructed to go to the nearest emergency department if symptoms worsen. In the
interim, the inhaled corticosteroid regimen should continue.
airway remodelling variable medium
Pathological changes affecting lung tissues as a result of persistent inflammation, causing a persistent
irreversible airway obstruction.[97] This obstruction resembles that in COPD and may progressively
worsen, limiting the activity of the patient.[98]
Those with more severe asthma may have a higher predilection for airway remodelling.
It is unknown what percentages have airway remodelling and, of those with remodelling, how many
develop COPD.
oral candidiasis secondary to use of inhaled variable medium

corticosteroids
The most common complication of inhaled corticosteroids is thrush, often prevented by the use of a spacer
tube, and rinsing, gargling, and spitting after inhaler use.
dysphonia secondary to use of inhaled corticosteroids variable medium
Another complication of inhaled corticosteroids is dysphonia (i.e., laryngeal muscle spasm causing an
abnormal voice), which can be prevented by changing the type of the inhaler.
oesophageal candidiasis secondary to use of inhaled variable low

corticosteroids
On rare occasions, this may occur secondary to use of inhaled corticosteroids.
HIV serologies should be checked.
Treat with appropriate antifungal agents (e.g., fluconazole).
Prognosis
Long-term effects
Although it has been assumed that airway inflammation and airway remodelling have a cause and
effect relationship, longitudinal evidence suggests that remodelling is an independent parallel process,
unresponsive to anti-inflammatory medication such as inhaled corticosteroids. Longitudinal follow-up of
45
childhood asthma into adulthood suggests that in some asthma patients remodelling commences early in
the disease process leading to fixed airflow obstruction. These cohort studies from general populations
in Australia and New Zealand have reproducibly shown that in children with persistent asthma symptoms,
most deficits in lung function growth have already occurred by 6 to 9 years of age,[89] [90] with a modest
FOLLOW UP
further effect of asthma on lung function thereafter. This is consistent with adult data, where a longitudinal
study of more than 9000 subjects found that asthmatic non-smokers had reduced FEV1 at 19 years of age
when compared with values in non-asthmatic non-smokers, and showed only minimal additional decrease
thereafter.[91] This suggests that airway remodelling with irreversible airflow obstruction occurs early with
persistent childhood asthma, but is a stable physiological phenotype thereafter. However, an accelerated
decline in lung function has also been observed in chronic severe asthma, particularly in association with
frequent and severe exacerbations.[92] [93]
Life expectancy
The life expectancy of people with controlled asthma is similar to that for the general population.
Impact of inhaled corticosteroids (ICS)

ICS provide clinical and laboratory improvement to the patient. If the steroids are discontinued, symptoms
recur and pulmonary function studies return to the initial abnormality. Treatment with ICS, although not
disease modifying, provide an additional anti-inflammatory effect. In other words, the lung inflammation is
reduced only while the patient is on the ICS, and once stopped, the inflammatory process returns. When
optimally controlled, asthma attacks decrease in frequency. Some patients will have no asthma attacks, and
others have continued attacks when exposed to precipitating agents.
Asthma in adults Guidelines
Diagnostic guidelines
Europe
British guideline on the management of asthma: a national clinical guideline

Published by: Scottish Intercollegiate Guidelines Network Last published: 2016
International
Global strategy for asthma management and prevention

Published by: Global Initiative for Asthma Last published: 2016
International ERS/ATS guidelines on definition, evaluation and treatment of

severe asthma
GUIDELINES
Published by: European Respiratory Society; American Thoracic Last published: 2014
Society
North America
CTS 2012 guideline update: diagnosis and management of asthma in

preschoolers, children and adults
Published by: Canadian Thoracic Society Last published: 2012
Guidelines for the diagnosis and management of asthma: expert panel report
3
Published by: National Heart, Lung, and Blood Institute Last published: 2007
Treatment guidelines
Europe
British guideline on the management of asthma: a national clinical guideline

Published by: Scottish Intercollegiate Guidelines Network Last published: 2016
Omalizumab for the treatment of severe persistent allergic asthma

Published by: National Institute for Health and Care Excellence Last published: 2013
Inhaled corticosteroids for the treatment of chronic asthma in adults and in

children aged 12 years and over
Published by: National Institute for Health and Care Excellence Last published: 2008
47
Asthma in adults Guidelines
Europe
A systematic review to examine the impact of psycho-educational

interventions on health outcomes and costs in adults and children with
difficult asthma
Published by: Health Technology Assessment NHS R&D HTA Last published: 2005
Programme
International
Global strategy for asthma management and prevention

Published by: Global Initiative for Asthma Last published: 2016
International ERS/ATS guidelines on definition, evaluation and treatment of

severe asthma
GUIDELINES
Published by: European Respiratory Society; American Thoracic Last published: 2014
Society
An official American Thoracic Society/European Respiratory Society

statement: asthma control and exacerbations: standardizing endpoints for
clinical asthma trials and clinical practice
Published by: American Thoracic Society; European Respiratory Last published: 2009
Society
North America
CTS 2012 guideline update: diagnosis and management of asthma in

preschoolers, children and adults
Published by: Canadian Thoracic Society Last published: 2012
Guidelines for the diagnosis and management of asthma: expert panel report
3
Published by: National Heart, Lung, and Blood Institute Last published: 2007
Consultation and referral guidelines citing the evidence: how the allergist-
immunologist can help
Published by: American Academy of Allergy, Asthma and Immunology Last published: 2006
Chronic cough due to asthma: ACCP evidence-based clinical practice

guidelines
Published by: American College of Chest Physicians Last published: 2006
At taining optimal asthma control: a practice parameter

Published by: Joint Council of Allergy, Asthma and Immunology Last published: 2005
Asthma in adults Evidence scores
Evidence scores
1. Symptom severity: there is medium-quality evidence that use of short-acting beta agonists (SABA) 'as
needed' was equally effective as regular use in reducing exacerbations and at improving daytime and
night-time symptoms, and that regular use of a SABA and 'as-needed' SABA were equally effective at
improving lung function in people with chronic asthma.
Evidence level B: Randomized controlled trials (RCTs) of <200 participants, methodologically
flawed RCTs of >200 participants, methodologically flawed systematic reviews (SRs) or good quality
observational (cohort) studies.
2. Symptom severity: there is medium-quality evidence that low-dose inhaled corticosteroids were
more effective than placebo at improving symptoms and at reducing the need for short-acting
bronchodilators in people with mild, moderate, or severe asthma. Low-dose inhaled corticosteroids
were also more effective than placebo at improving lung function (FEV1 and peak expiratory flow rate
[PEFR]) in people with asthma.
3. Symptom severity: there is medium-quality evidence that adding a leukotriene-receptor antagonist

was more effective than adding placebo at reducing daytime and night-time symptoms, at reducing
beta-2 agonist use, and at improving FEV1, but was less effective than adding inhaled corticosteroids
at increasing symptom-free days, reducing the need for systemic corticosteroids, reducing the need for
rescue medication, or improving FEV1.
4. Symptom severity: there is medium-quality evidence that adding long-acting beta-2 agonists (LABAs)
to inhaled corticosteroids was more effective than increasing the dose of inhaled corticosteroids at
improving symptoms, increasing symptom-free days, reducing the need for rescue medicines at 3 to
6 months, and improving FEV1 and peak expiratory flow rate (PEFR) in people with poorly controlled
asthma. Salmeterol has been associated with asthma-related mortality (possibly by making asthma
episodes worse), which has been supported by regulatory warnings. Thus, LABAs are not a substitute
for controller medications (corticosteroids) at appropriate doses, and should always be used with
inhaled corticosteroids.
EVIDENCE SCORES
5. Symptom severity: there is medium-quality evidence that leukotriene antagonists plus inhaled
corticosteroids were no more effective than increasing inhaled corticosteroids at decreasing daytime
49
Asthma in adults Evidence scores
symptoms and days with asthma exacerbations or nocturnal wakening, or at improving peak expiratory
flow rate (PEFR) in people with mild-to-moderate persistent asthma.
6. Lung function: there is poor-quality evidence that adding theophylline to low-dose corticosteroids
may be more effective than adding placebo at improving morning and evening peak expiratory flow
rate (PEFR) in people with persistent asthma poorly controlled with inhaled corticosteroids. Adding
theophylline was as effective as adding a long-acting beta-2 agonist (LABA) to inhaled corticosteroids
at improving FEV1 in people with poorly controlled moderate and persistent asthma.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.
7. Symptom severity: there is medium-quality evidence that adding a long-acting beta-2 agonist (LABA)
to inhaled corticosteroids was more effective than inhaled corticosteroids alone at reducing the need
for systemic corticosteroids in people with poorly controlled asthma and at improving FEV1 and peak
expiratory flow rate (PEFR) in people with poorly controlled asthma.
8. Lung function: there is poor-quality evidence to support the use of intravenous magnesium in people
with severe acute asthma. Further studies are needed.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.
EVIDENCE SCORES
Asthma in adults References
Key articles
• National Institutes of Health; National Heart, Lung, and Blood Institute, National Asthma Education and
REFERENCES
Prevention Program. Expert panel report 3: Guidelines for the diagnosis and management of asthma.
August 2007. http://www.nhlbi.nih.gov/ (last accessed 11 October 2016). Full text
• Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation
of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med.
2011;184:602-615. Full text Abstract
• British Thoracic Society/Scottish Intercollegiate Guidelines Network. SIGN 153: British guideline on the
management of asthma. A national clinical guideline. September 2016 [internet publication]. Full text
• Joos S, Miksch A, Szecsenyi J, et al. Montelukast as add-on therapy to inhaled corticosteroids in the
treatment of mild to moderate asthma: a systematic review. Thorax. 2008;63:453-462. Abstract
• Rodrigo GJ, Moral VP, Marcos LG, et al. Safety of regular use of long-acting beta agonists as
monotherapy or added to inhaled corticosteroids in asthma. A systematic review. Pulm Pharmacol
Ther. 2009;22:9-19. Abstract
• Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with
uncontrolled asthma. N Engl J Med. 2010;363:1715-1726. Full text Abstract
• Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and safety of subcutaneous omalizumab vs
placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review.
Chest. 2011;139:28-35. Full text Abstract
• Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the
management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev.
2012;(5):CD002314. Full text Abstract
• Chauhan BF, Ducharme FM. Addition to inhaled corticosteroids of long-acting beta2-agonists versus
anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev. 2014;(1):CD003137. Full text
Abstract
• Masoli M, Weatherall M, Holt S, et al. Inhaled fluticasone propionate and adrenal effects in adult
asthma: systematic review and meta-analysis. Eur Respir J. 2006 Nov;28(5):960-7. Full text Abstract
• Ortega HG, Liu MC, Pavord ID, et al; MENSA Investigators. Mepolizumab treatment in patients with
severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207. Full text Abstract
• Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J
Med. 2011;365:1088-1098. Full text Abstract
References
51
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59
Contributors:
// Authors:
Irwani Ibrahim, MBBS, FRCSEd, MPH, FAMS

Consultant
Emergency Department, National University Hospital, Singapore
DISCLOSURES: II declares that she has no competing interests.
Kay Choong See, MBBS, MRCP, MPH, EDIC, FCCP

Head and Consultant
Division of Respiratory and Critical Care Medicine, National University Hospital, Singapore
DISCLOSURES: KCS declares that he has no competing interests.
// Acknowledgements:
Dr Irwani Ibrahim and Dr Kay Choong See would like to gratefully acknowledge Dr Francis Thien and Dr
Catherine Weiler, previous contributors to this monograph. FT and CW declare that they have no competing
interests.
// Peer Reviewers:
Javed Sheikh, MD
Clinical Director
Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center/Harvard Medical School,
Boston, MA
DISCLOSURES: JS is a consultant for Aventis, GSK, and Novartis/Genentech; is on the Speakers Bureau
for Merck, Aventis, GSK, AstraZeneca, Pfizer, Novartis/Genentech, Inspire, and UCB; has had research
sponsored by GSK; is an expert witness at Haemonetics; and has received publication honorarium at
Emedicine.
Sheree M.S. Smith, PhD

Research Manager
Imperial College Healthcare Trust, NHLI Airways Division, Imperial College London (Honorary) Respiratory
Research, Chest & Allergy, St Mary's Hospital, London, UK
DISCLOSURES: SMSS declares that she has no competing interests.
Neil Thomson, MBChB, MD, FRCP

Professor of Respiratory Medicine
Respiratory Medicine Section, Division of Immunology, Infection & Inflammation, University of Glasgow,
Glasgow, UK
DISCLOSURES: NT declares that he has no competing interests.

Asthma in Adults: The Right Clinical Information, Right Where It's Needed

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Last updated: Jan 29, 2018

◊ Some patients may develop progressive, irreversible obstructive lung disease.

Patients' genetic make-up may predispose them to hyper-responsiveness to environmental aetiological

Patients with known allergic asthma should avoid precipitants.

Step-by-step diagnostic approach

exercise, eucapnic hyperventilation, inhaled hypertonic saline, mannitol, or adenosine monophosphate)

[VIDEO: Peak flow measurement animated demonstration ]

History & examination factors

recent upper respiratory tract infection (common)

expiratory wheezes (common)

nasal polyposis (common)

• FEV1 may be used for subsequent follow-up at least once a year.

[VIDEO: Peak flow measurement animated

Other tests to consider

Condition Differentiating signs / Differentiating tests

Condition Differentiating signs / Differentiating tests

Tracheomalacia • Symptoms are usually • The sensitivity of plain

Vascular ring • Wheezing, shortness of • CT chest with contrast:

Foreign body aspiration • Wheezing, shortness of • CXR, CT chest, or

Condition Differentiating signs / Differentiating tests

Alpha-1 antitrypsin • Wheezing, resistant to • Testing for the alpha-1

COPD • History of smoking. • PFTs with residual volume

Bronchiectasis • Dyspnoea, cough, and • High-resolution CT chest:

recurrent pulmonary wall thickening.

Pulmonary embolism • Patients have a wide variety • Risk stratification with

Condition Differentiating signs / Differentiating tests

• Symptoms ≤2 times a week

• Symptoms >2 times a week but <1 time a day

Step-by-step treatment approach

Stepwise therapy for long-term management

Education and environmental control

Step 1: mild intermit tent and exercise-induced asthma

• Symptoms ≤2 times a week

Step 2: mild persistent

• Symptoms >2 times a week but <1 time a day

All patients should have access to quick-relief SABAs.

Step 3: moderate persistent

ICS with either an LTRA,[55] 5[B]Evidence theophylline,6[C]Evidence or zileuton.

All patients should have access to quick-relief SABAs.

Step 6 adds oral corticosteroids to existing treatments.

All patients should have access to quick-relief SABAs.

[VIDEO: Peak flow measurement animated demonstration ]

Treatment details overview

exercise-induced asthma needed

step 2: mild persistent 1st low-dose inhaled corticosteroid (ICS)

2nd leukotriene-receptor antagonist (LTRA)

adjunct short-acting beta agonist (SABA) as

step 3: moderate persistent 1st low-dose inhaled corticosteroid (ICS)

plus long-acting beta agonist (LABA)

adjunct short-acting beta agonist (SABA) as

step 3: moderate persistent 1st medium-dose inhaled corticosteroid (ICS)

adjunct short-acting beta agonist (SABA) as

2nd low-dose inhaled corticosteroid (ICS) +

adjunct short-acting beta agonist (SABA) as

step 4: severe persistent 1st medium-dose inhaled corticosteroid (ICS)

plus long-acting beta agonist (LABA) or

adjunct short-acting beta agonist (SABA) as

2nd medium-dose inhaled corticosteroid (ICS)

adjunct short-acting beta agonist (SABA) as

step 5: severe persistent, 1st high-dose inhaled corticosteroid (ICS)

plus long-acting beta agonist (LABA) or