Asthma Management Handbook

Identifying severe asthma in adults and adolescents

Recommendations

If a patient continues to experience poor control of asthma, frequent flare-ups, or poor quality of life due to asthma, despite regular treatment with a high dose of an inhaled corticosteroid plus a long-acting beta2 agonist, make a full assessment to rule out common problems (including poor inhaler technique and suboptimal adherence) before applying the label of severe asthma.

Note: Severe asthma is defined as asthma that remains uncontrolled despite regular treatment with high-dose inhaled corticosteroids plus long-acting beta2 agonist or with maintenance oral corticosteroids, or asthma that requires this level of treatment (Step 4) to prevent it becoming uncontrolled.

Table. Definitions of ICS dose levels in adults

Inhaled corticosteroid Daily dose (microg)
Low Medium High
Beclometasone dipropionate † 100–200 250–400 >400
Budesonide 200–400 500–800 >800
Ciclesonide 80–160 240–320 >320
Fluticasone furoate* 100 200
Fluticasone propionate 100–200 250–500 >500

† Dose equivalents for Qvar (TGA-registered CFC-free formulation of beclometasone dipropionate).

*Fluticasone furoate is not available as a low dose. TGA-registered formulations of fluticasone furoate contain a medium or high dose of fluticasone furoate and should only be prescribed as one inhalation once daily.

Note: The potency of generic formulations may differ from that of original formulations. Check TGA-approved product information for details.

Sources

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

GlaxoSmithKline Australia Pty Ltd. Product Information: Breo (fluticasone furoate; vilanterol) Ellipta. Therapeutic Goods Administration, Canberra, 2014. Available from: https://www.ebs.tga.gov.au/

GlaxoSmithKline Australia Pty Ltd. Product Information: Arnuity (fluticasone furoate) Ellipta. Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/

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Table. Definition of levels of recent asthma symptom control in adults and adolescents (regardless of current treatment regimen)

Good control

Partial control

Poor control

All of:

  • Daytime symptoms ≤2 days per week
  • Need for SABA reliever ≤2 days per week
  • No limitation of activities
  • No symptoms during night or on waking

One or two of:

  • Daytime symptoms >2 days per week
  • Need for SABA reliever >2 days per week
  • Any limitation of activities
  • Any symptoms during night or on waking

Three or more of:

  • Daytime symptoms >2 days per week
  • Need for SABA reliever >2 days per week
  • Any limitation of activities
  • Any symptoms during night or on waking

SABA: short-acting beta2-agonist

† SABA, not including doses taken prophylactically before exercise. (Record this separately and take into account when assessing management.)

Note: Recent asthma symptom control is based on symptoms over the previous 4 weeks.

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Figure. Stepped approach to adjusting asthma medication in adults and adolescents Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/figure/show/31

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Confirm the diagnosis of asthma by:

  • reviewing documentation of demonstrated variable expiratory airflow limitation
  • identifying and investigating any signs and symptoms that could suggest an alternative diagnosis or comorbidity (e.g. upper airway dysfunction, bronchiectasis, cardiac disease, de-conditioning).

Table. Findings that increase or decrease the probability of asthma in adults

Asthma is more likely to explain the symptoms if any of these apply

Asthma is less likely to explain the symptoms if any of these apply

More than one of these symptoms:

  • wheeze
  • breathlessness
  • chest tightness
  • cough

Symptoms recurrent or seasonal

Symptoms worse at night or in the early morning

History of allergies (e.g. allergic rhinitis, atopic dermatitis)

Symptoms obviously triggered by exercise, cold air, irritants, medicines (e.g. aspirin or beta blockers), allergies, viral infections, laughter

Family history of asthma or allergies

Symptoms began in childhood

Widespread wheeze audible on chest auscultation

FEV1 or PEF lower than predicted, without other explanation

Eosinophilia or raised blood IgE level, without other explanation

Symptoms rapidly relieved by a SABA bronchodilator

Dizziness, light-headedness, peripheral tingling

Isolated cough with no other respiratory symptoms

Chronic sputum production

No abnormalities on physical examination of chest when symptomatic (over several visits)

Change in voice

Symptoms only present during upper respiratory tract infections

Heavy smoker (now or in past)

Cardiovascular disease

Normal spirometry or PEF when symptomatic (despite repeated tests)

Adapted from:

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

British Thoracic Society (BTS) Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. A national clinical guideline. BTS/SIGN, Edinburgh; 2012. Available from: https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline/.

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Table. Differential diagnosis of severe asthma in adults

Clinical feature

Alternative diagnoses or comorbidity*

Dyspnoea prominent

Obesity and inactivity with deconditioning

COPD

Alpha-1 antitrypsin deficiency

Heart disease

Pulmonary hypertension

Central airway stenosis

Tracheobronchomalacia

Interstitial lung disease

Bronchiolitis obliterans

Lung cancer

Tracheal stricture

Pulmonary embolism

Cough prominent

Upper airway dysfunction

Upper airway cough syndrome

Adverse drug reaction (e.g. angiotensin-converting enzyme inhibitors, beta-adrenergic blockers)

Bronchiolitis obliterans

Lung cancer

Herpetic tracheobronchitis

Tracheal stricture
Chronic sputum production

COPD

Bronchiectasis

Allergic bronchopulmonary aspergillosis

Cystic fibrosis
History of exposure to tobacco smoke/biomass fuels

COPD

Lung cancer
Dizziness or lightheadedness

Dysfunctional breathing/hyperventilation syndrome

Tachyarrhythmias
Sudden-onset symptoms

Vocal cord dysfunction (paradoxical vocal cord movement)

Panic attacks with hyperventilation

Pulmonary embolism
Irritative triggers, tightness in upper chest/neck, dysphonia Vocal cord dysfunction (paradoxical vocal cord movement)
Symptoms triggered by food or posture Symptomatic gastro-oesophageal reflux disease
Night waking

Obstructive sleep apnoea

Symptomatic gastro-oesophageal reflux disease

Heart failure
Chest crackles

Bronchiectasis

Heart failure

Interstitial lung disease

Hypersensitivity pneumonitis
Respiratory symptoms with sinusitis and/or nasal polyposis#

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Aspirin-exacerbated respiratory disease
Respiratory symptoms with gastrointestinal symptoms

Cystic fibrosis

Hypereosinophilic syndrome
Onset related to menstrual cycle Premenstrual (catamenial) asthma
Eosinophilia

Chronic eosinophilic pneumonia

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Hypereosinophilic syndrome

Hypersensitivity pneumonia

Parasitic infection

*Most of the differential diagnoses listed can also occur with asthma.

#especially if evidence of other organ involvement (skin, mononeuritis multiplex, cardiac)

Sources: Israel and Reddel (2017),1 Chung et al (2014),2 Maltby et al (2016),3 Papi et al (2018),4 FitzGerald et al (2017)5

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Reassess whether the person’s current symptoms are likely to be due to asthma, or likely due to a comorbidity or alternative diagnosis.

Note: Consider contributing factors like anxiety, obesity, symptomatic gastroesophageal reflux disease, rhinosinusitis, hormonal influences (e.g. premenstrual asthma, menarche, menopause, thyroid disorders).

Table. Differential diagnosis of severe asthma in adults

Clinical feature

Alternative diagnoses or comorbidity*

Dyspnoea prominent

Obesity and inactivity with deconditioning

COPD

Alpha-1 antitrypsin deficiency

Heart disease

Pulmonary hypertension

Central airway stenosis

Tracheobronchomalacia

Interstitial lung disease

Bronchiolitis obliterans

Lung cancer

Tracheal stricture

Pulmonary embolism

Cough prominent

Upper airway dysfunction

Upper airway cough syndrome

Adverse drug reaction (e.g. angiotensin-converting enzyme inhibitors, beta-adrenergic blockers)

Bronchiolitis obliterans

Lung cancer

Herpetic tracheobronchitis

Tracheal stricture
Chronic sputum production

COPD

Bronchiectasis

Allergic bronchopulmonary aspergillosis

Cystic fibrosis
History of exposure to tobacco smoke/biomass fuels

COPD

Lung cancer
Dizziness or lightheadedness

Dysfunctional breathing/hyperventilation syndrome

Tachyarrhythmias
Sudden-onset symptoms

Vocal cord dysfunction (paradoxical vocal cord movement)

Panic attacks with hyperventilation

Pulmonary embolism
Irritative triggers, tightness in upper chest/neck, dysphonia Vocal cord dysfunction (paradoxical vocal cord movement)
Symptoms triggered by food or posture Symptomatic gastro-oesophageal reflux disease
Night waking

Obstructive sleep apnoea

Symptomatic gastro-oesophageal reflux disease

Heart failure
Chest crackles

Bronchiectasis

Heart failure

Interstitial lung disease

Hypersensitivity pneumonitis
Respiratory symptoms with sinusitis and/or nasal polyposis#

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Aspirin-exacerbated respiratory disease
Respiratory symptoms with gastrointestinal symptoms

Cystic fibrosis

Hypereosinophilic syndrome
Onset related to menstrual cycle Premenstrual (catamenial) asthma
Eosinophilia

Chronic eosinophilic pneumonia

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Hypereosinophilic syndrome

Hypersensitivity pneumonia

Parasitic infection

*Most of the differential diagnoses listed can also occur with asthma.

#especially if evidence of other organ involvement (skin, mononeuritis multiplex, cardiac)

Sources: Israel and Reddel (2017),1 Chung et al (2014),2 Maltby et al (2016),3 Papi et al (2018),4 FitzGerald et al (2017)5

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0
 

Recheck adherence to inhaled corticosteroid-based preventer.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Recheck inhaler technique.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Assess use of short-acting beta2 agonist reliever to identify overuse:

  • Ask how many puffs taken per day.
  • Ask how long reliever puffer lasts.
  • Check prescribing records.
  • Ask if patient also uses non-prescription (‘over-the counter’) reliever.
  • Dispensing of 3 or more canisters in a year (average 1.6 puffs per day) is associated with increased risk of flare-ups. Dispensing 12 or more canisters in a year (average 6.6 puffs per day) is associated with increased risk of asthma death.

Note: My Health Record may include over-the-counter dispensing information for reliever

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Assess any comorbid conditions that could be contributing to respiratory symptoms, poor quality of life or flare-ups, or compromising self-management, such as allergic rhinitis, chronic rhinosinusitis, symptomatic gastro-oesophageal reflux disease, obstructive sleep apnoea, obesity, deconditioning, mental health problems (e.g. anxiety, depression) or other psychosocial problems, or upper airway dysfunction.

Table. Differential diagnosis of severe asthma in adults

Clinical feature

Alternative diagnoses or comorbidity*

Dyspnoea prominent

Obesity and inactivity with deconditioning

COPD

Alpha-1 antitrypsin deficiency

Heart disease

Pulmonary hypertension

Central airway stenosis

Tracheobronchomalacia

Interstitial lung disease

Bronchiolitis obliterans

Lung cancer

Tracheal stricture

Pulmonary embolism

Cough prominent

Upper airway dysfunction

Upper airway cough syndrome

Adverse drug reaction (e.g. angiotensin-converting enzyme inhibitors, beta-adrenergic blockers)

Bronchiolitis obliterans

Lung cancer

Herpetic tracheobronchitis

Tracheal stricture
Chronic sputum production

COPD

Bronchiectasis

Allergic bronchopulmonary aspergillosis

Cystic fibrosis
History of exposure to tobacco smoke/biomass fuels

COPD

Lung cancer
Dizziness or lightheadedness

Dysfunctional breathing/hyperventilation syndrome

Tachyarrhythmias
Sudden-onset symptoms

Vocal cord dysfunction (paradoxical vocal cord movement)

Panic attacks with hyperventilation

Pulmonary embolism
Irritative triggers, tightness in upper chest/neck, dysphonia Vocal cord dysfunction (paradoxical vocal cord movement)
Symptoms triggered by food or posture Symptomatic gastro-oesophageal reflux disease
Night waking

Obstructive sleep apnoea

Symptomatic gastro-oesophageal reflux disease

Heart failure
Chest crackles

Bronchiectasis

Heart failure

Interstitial lung disease

Hypersensitivity pneumonitis
Respiratory symptoms with sinusitis and/or nasal polyposis#

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Aspirin-exacerbated respiratory disease
Respiratory symptoms with gastrointestinal symptoms

Cystic fibrosis

Hypereosinophilic syndrome
Onset related to menstrual cycle Premenstrual (catamenial) asthma
Eosinophilia

Chronic eosinophilic pneumonia

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)

Hypereosinophilic syndrome

Hypersensitivity pneumonia

Parasitic infection

*Most of the differential diagnoses listed can also occur with asthma.

#especially if evidence of other organ involvement (skin, mononeuritis multiplex, cardiac)

Sources: Israel and Reddel (2017),1 Chung et al (2014),2 Maltby et al (2016),3 Papi et al (2018),4 FitzGerald et al (2017)5

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Assess and manage exposure to asthma triggers at home or work (e.g. cigarette smoke, allergens, irritants, infections, moulds/dampness, indoor or outdoor air pollution).

Table. Summary of asthma triggers Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/52

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Consider the possible presence of aspirin-exacerbated respiratory disease. If suspected, refer for assessment.

Note: The syndrome of aspirin-exacerbated respiratory disease is characterised by airway inflammation including asthma, nasal polyposis, and flare-ups (which may be severe) in response to NSAIDs.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Optimise the person’s treatment regimen and review after each change, e.g:

  • For a patient taking inhaled corticosteroid plus a long-acting beta2 agonist as maintenance therapy with as-needed short-acting beta2 agonist as reliever, consider changing to low-dose budesonide plus formoterol as single maintenance-and-reliever therapy to reduce the risk of flare-ups.
  • Consider a trial of add-on tiotropium by mist inhaler.
  • Consider a trial of high-dose inhaled corticosteroids for 3–6 months.
  • Consider a trial of add-on montelukast.

Cease ineffective therapies.

Note: Review inhaler technique and adherence before trialling changes to the treatment regimen.

There is very little evidence supporting the use of add-on montelukast for severe asthma. Limited evidence supports its use in the management of aspirin-exacerbated respiratory disease.

  • If using an inhaled corticosteroid and a long-acting beta2 agonist in separate inhalers, warn the patient about the serious risk of stopping the inhaled corticosteroid, and give clear written instructions not to use the long-acting beta2 agonist on its own.
  • Warn patients about potential neuropsychiatric effects of montelukast.

Note: PBS status as at March 2019:

Adults: Tiotropium is subsidised by the PBS when used in combination with maintenance ICS+LABA treatment, for people with ≥ one documented severe exacerbation that required systemic corticosteroids in the previous 12 months despite maintenance treatment with inhaled corticosteroid (equivalent to 800 microg budesonide/day or higher) in combination with a long-acting beta2 agonist, and correct inhaler technique has been assessed, demonstrated and documented.

Adolescents aged up to 17 years: Tiotropium is subsidised by the PBS when used in combination with maintenance ICS+LABA treatment, for patients with severe asthma treated by (or in consultation with) a specialist, with frequent moderate exacerbations or ≥ one documented severe exacerbation that required systemic corticosteroids in the previous 12 months despite maintenance treatment with a medium-to-high dose of inhaled corticosteroid in combination with a long-acting beta2 agonist, and correct inhaler technique has been assessed, demonstrated and documented (see PBS for details).

PBS status as at March 2019: Montelukast treatment is not subsidised by the PBS for people aged 15 years or over. However, generic formulations are available as non-PBS prescriptions at lower cost to patients than in the past.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Provide every patient with an individualised written asthma action plan and update it regularly (at least yearly, and whenever treatment is changed).

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Identify patients with possible severe asthma who might benefit from monoclonal antibody therapy, and offer referral for specialist assessment without delay (after checking inhaler technique and adherence):

  • Add-on treatment with omalizumab can be considered for adults and adolescents with uncontrolled severe allergic asthma.
  • Add-on treatment with benralizumab or mepolizumab can be considered for adults and adolescents aged 12 years and over with uncontrolled severe eosinophilic asthma.

Note: PBS status as at March 2019: In addition to specific criteria for each agent, all the following must be documented before an adult or adolescent is eligible for any monoclonal antibody asthma treatment:

  • asthma present for at least 1 year

  • diagnosis of asthma (specific criteria apply) confirmed and documented by a specialist (respiratory physician, clinical immunologist, allergist or general physician experienced in the management of patients with severe asthma)

  • treatment by the same specialist for at least 6 months or asthma diagnosis by a multidisciplinary severe asthma clinic team

  • inadequate asthma control despite documentaed adherence to optimised standard treatment (that includes high-dose inhaled corticosteroid plus long-acting beta2 agonist for at least 12 months), with at least one severe flare-up requiring hospitalisation or systemic corticosteroids in the past year.

Note: Tests to determine severe asthma phenotype, determine eligibility (e.g. skin prick testing, blood eosinophil count) and predict whether monoclonal antibody therapy is likely to be effective (e.g. FeNO, eosinophil count) need not be completed in primary care – it is preferable that these are arranged by the specialist.

Monoclonal antibody treatments for severe asthma can only be prescribed for patients attending a public hospital or approved private hospital.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to named source(s):

  • Bleecker et al. 20166
  • FitzGerald et al. 20167
  • Nair et al. 20178
  • Wang et al, 20169
  • Bel et al. 201410
  • Ortega et al. 201411
  • Lai et al. 201512
  • Norman et al. 201313
  • Normansell et al. 201414
  • Abraham et al. 201615
  • Gibson et al. 201616

Last reviewed version 2.0

Refer a patient with severe asthma to a specialist for assessment if:

  • prolonged high-dose inhaled corticosteroids are needed to control asthma
  • the person requires maintenance oral corticosteroid treatment or frequently requires courses of oral corticosteroids
  • despite maintenance preventer treatment, the person has been using frequent short-acting beta2 agonist reliever for a prolonged period (e.g. 6–8 puffs per day for several weeks), and common causes of poor asthma control have been investigated and ruled out
  • the person experiences frequent or sudden flare-ups
  • food allergy is present or suspected.
  • For most patients, high doses of inhaled corticosteroids should be used for short periods only.

Note: Offer referral to a respiratory physician, if possible.

Offer referral to a severe asthma clinic for multidisciplinary care, if available.

If referral to a respiratory physician is not possible, refer to a general physician, allergist or clinical immunologist with expertise in managing severe asthma.

If specialist referral is not possible, obtain specialist advice.

Table. Definitions of ICS dose levels in adults

Inhaled corticosteroid Daily dose (microg)
Low Medium High
Beclometasone dipropionate † 100–200 250–400 >400
Budesonide 200–400 500–800 >800
Ciclesonide 80–160 240–320 >320
Fluticasone furoate* 100 200
Fluticasone propionate 100–200 250–500 >500

† Dose equivalents for Qvar (TGA-registered CFC-free formulation of beclometasone dipropionate).

*Fluticasone furoate is not available as a low dose. TGA-registered formulations of fluticasone furoate contain a medium or high dose of fluticasone furoate and should only be prescribed as one inhalation once daily.

Note: The potency of generic formulations may differ from that of original formulations. Check TGA-approved product information for details.

Sources

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

GlaxoSmithKline Australia Pty Ltd. Product Information: Breo (fluticasone furoate; vilanterol) Ellipta. Therapeutic Goods Administration, Canberra, 2014. Available from: https://www.ebs.tga.gov.au/

GlaxoSmithKline Australia Pty Ltd. Product Information: Arnuity (fluticasone furoate) Ellipta. Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

More information

What is severe asthma?

Definitions

Severe asthma is asthma that remains uncontrolled despite high-dose inhaled corticosteroids plus long-acting beta2 agonist (with correct inhaler technique and good adherence) or maintenance oral corticosteroids, or that requires such treatment to prevent it becoming uncontrolled.2

Severe asthma is sometimes also called ‘severe refractory asthma' or 'severe treatment-resistant asthma'. However, the introduction of monoclonal antibody therapies has demonstrated that significant improvements can be seen in asthma that was previously termed ‘refractory’.

Asthma is considered to be uncontrolled if any of the following are identified:

  • poor symptom control, e.g. during previous 4 weeks any of:
    • symptoms during night or on waking
    • limitation of activities due to asthma
    • daytime symptoms on more than 2 days per week
    • need for short-acting beta2 agonist reliever on more than 2 days per week (not including doses taken prophylactically before exercise).
  • frequent severe flare-ups (e.g. more than one flare-up requiring treatment with oral corticosteroids in the previous year)
  • serious flare-ups (e.g. hospital admission, intensive care unit admission, or mechanical ventilation in the previous year)
  • persistent airflow limitation (e.g. detected by spirometry).

Patients with severe asthma are a subgroup of those with difficult-to-treat asthma. Difficult-to-treat asthma is defined as asthma that remains uncontrolled despite treatment with a high dose of an inhaled corticosteroid combined with a long-acting beta2 agonist.

Not all patients with difficult-to-treat asthma have severe asthma. Difficult-to-treat asthma includes asthma that is uncontrolled due to suboptimal adherence, inappropriate or incorrect use of medicines, environmental triggers or comorbidities. Patients whose asthma control improves rapidly after such problems are corrected are not considered to have severe asthma.2

Prevalence

Severe asthma is uncommon. Less than 4% of adults with asthma have severe asthma.17

Description

Severe asthma appears to be a distinct disease (or group of diseases) with different pathobiology from that of milder forms of asthma. It is rare for mild asthma to progress to severe asthma.18

Severe asthma imposes a high burden of disease due to symptoms, flare-ups, medication-related adverse effects and costs.1, 19

Bronchiectasis, granulomas and other auto-immune disease processes can coexist with severe asthma.18, 20 Aspirin-exacerbated respiratory disease can present as severe asthma.

Patterns of airway inflammation vary among people with severe asthma,4 which suggests that the underlying pathophysiology varies.

Inflammatory patterns identified in adults in research studies include eosinophilic (elevated sputum eosinophil count), neutrophilic (elevated sputum neutrophil count), mixed (elevated sputum eosinophil and neutrophil counts) and paucigranulocytic (sputum eosinophil and neutrophil counts within normal range).21 However, these tests are not routinely available in practice to guide treatment.

Some patients with severe asthma show sustained eosinophilia on blood tests despite good adherence to treatment with high doses of inhaled corticosteroids18, 22

Current research aims to predict which treatments will be most effective in an individual according to the findings of a range clinical investigations (e.g. sputum cell counts, peripheral blood white cell counts, fraction of exhaled nitric oxide [FeNO]) and on other clinical features such as age of asthma onset, relationship of allergies to asthma symptoms or presence of nasal polyposis. Few studies have been conducted to identify severe asthma phenotypes among children with severe asthma.4

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Correct use of inhaler devices

Checking and correcting inhaler technique is essential to effective asthma management.

Most patients with asthma or COPD do not use their inhalers properly,1, 4-7 and most have not had their technique checked or corrected by a health professional.

Incorrect inhaler technique when using maintenance treatments increases the risk of severe flare-ups and hospitalisation for people with asthma or COPD.1, 4, 5, 14, 22, 23

Poor asthma symptom control is often due to incorrect inhaler technique.24, 25

Incorrect inhaler technique when using inhaled corticosteroids increases the risk of local side effects like dysphonia and oral thrush.

The steps for using an inhaler device correctly differ between brands. Checklists of correct steps for each inhaler type and how-to videos are available from the National Asthma Council website.

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Adherence to preventer treatment: adults and adolescents

Most patients do not take their preventer medication as often as prescribed, particularly when symptoms improve, or are mild or infrequent. Whenever asthma control is poor despite apparently adequate treatment, poor adherence, as well as poor inhaler technique, are probable reasons to consider.

Poor adherence may be intentional and/or unintentional. Intentional poor adherence may be due to the person’s belief that the medicine is not necessary, or to perceived or actual adverse effects. Unintentional poor adherence may be due to forgetting or cost barriers.

Common barriers to the correct use of preventers include:

  • being unable to afford the cost of medicines or consultations to adjust the regimen
  • concerns about side effects
  • interference of the regimen with the person’s lifestyle
  • forgetting to take medicines
  • lack of understanding of the reason for taking the medicines
  • inability to use the inhaler device correctly due to physical or cognitive factors
  • health beliefs that are in conflict with the belief that the prescribed medicines are effective, necessary or safe (e.g. a belief that the prescribed preventer dose is ‘too strong’ or only for flare-ups, a belief that asthma can be overcome by psychological effort, a belief that complementary and alternative therapies are more effective or appropriate than prescribed medicines, mistrust of the health professional).

Adherence to preventers is significantly improved when patients are given the opportunity to negotiate the treatment regimen based on their goals and preferences.23

Assessment of adherence requires an open, non-judgemental approach.

Accredited pharmacists who undertake Home Medicines Reviews can assess adherence while conducting a review.

Table. Suggested questions to ask adults and older adolescents when assessing adherence to treatment

  1. Many people don’t take their medication as prescribed. In the last four weeks:
    • how many days a week would you have taken your preventer medication? None at all? One? Two? (etc).
    • ​how many times a day would you take it? Morning only? Evening only? Morning and evening? (or other)
    • each time, how many puffs would you take? One? Two? (etc).
  2. Do you find it easier to remember your medication in the morning, or the evening?

Source: Foster JM, Smith L, Bosnic-Anticevich SZ et al. Identifying patient-specific beliefs and behaviours for conversations about adherence in asthma. Intern Med J 2012; 42: e136-e44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21627747

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Definition of variable expiratory airflow limitation

Most of the tests for variable expiratory airflow limitation are based on showing variability in FEV1. While reduced FEV1 may be seen with many other lung diseases (or due to poor spirometric technique), a reduced ratio of FEV1 to FVC indicates airflow limitation.24 Normal FEV1/FVC values derived from population studies vary,2526 but are usually greater than:25

  • 0.85 in people aged up to 19 years
  • 0.80 in people aged 20–39 years
  • 0.75 in people aged 40–59 years
  • 0.70 in people aged 60–80 years.

In children, it is less useful to define expiratory airflow limitation according to a specific cut-off for FEV1/FVC ratio, because normal values in children change considerably with age.26

Some spirometers provide predicted normal values specific to age group. If these are available, a FEV1/FVC ratio less than the lower limit of normal (i.e. less than the 5th percentile of normal population) indicates airflow limitation.

Variable expiratory airflow limitation (beyond the range seen in healthy populations) can be documented if any of the following are recorded:

  • a clinically important increase in FEV1 (change in FEV1 of at least 200 mL and 12% from baseline for adults, or at least 12% from baseline for children) 10–15 minutes after administration of bronchodilator
  • clinically important variation in lung function (at least 20% change in FEV1) when measured repeatedly over time (e.g. spirometry on separate visits)
  • a clinically important reduction in lung function (decrease in FEV1 of at least 200 mL and 12% from baseline on spirometry, or decrease in peak expiratory flow rate by at least 20%) after exercise (formal laboratory-based exercise challenge testing uses different criteria for exercise-induced bronchoconstriction)
  • a clinically important increase in lung function (at least 200 mL and 12% from baseline) after a trial of 4 or more weeks of treatment with an inhaled corticosteroid
  • clinically important variation in peak expiratory flow (diurnal variability of more than 10%)
  • a clinically important reduction in lung function (15–20%, depending on the test) during a test for airway hyperresponsiveness (exercise challenge test or bronchial provocation test) measured by a respiratory function laboratory.

Notes

Patients referred to a respiratory function laboratory may be asked not to take certain medicines within a few hours to days before a spirometry visit.

A clinically important increase or decrease in lung function is defined as a change in FEV1 of at least 200 mL and 12% from baseline for adults, or at least 12% from baseline for children, or a change in peak expiratory flow rate of at least 20% on the same meter.2724 A clinically important increase in FVC after administering bronchodilator may also indicate reversible airflow limitation, but FVC is a less reliable measure in primary care because FVC may vary due to factors such as variation in inspiratory volume or expiratory time.

The finding of ‘normal’ lung function during symptoms reduces the probability that a patient has asthma, but a clinically important improvement in response to bronchodilator or inhaled corticosteroid can occur in patients whose baseline value is within the predicted normal range.

The greater the variation in lung function, the more certain is the diagnosis of asthma. However, people with longstanding asthma may develop fixed airflow limitation.

Reversibility in airflow limitation may not be detected if the person is already taking a long-acting beta2 agonist or inhaled corticosteroid.

Airflow limitation can be transient and does not necessarily mean that the person has asthma (e.g. when recorded during a severe acute infection of the respiratory tract). Ideally, airflow limitation should be confirmed when the patient does not have a respiratory tract infection. Reduction in lung function during a respiratory tract infection with improvement in lung function after its resolution, commonly occurs in people with asthma, but can also be seen in patients with COPD or in healthy people without either asthma or COPD.28,29

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Spirometry in diagnosis and monitoring

Spirometry is the best lung function test for diagnosing asthma and for measuring lung function when assessing asthma control. Spirometry can:

  • detect airflow limitation
  • measure the degree of airflow limitation compared with predicted normal airflow (or with personal best)
  • demonstrate whether airflow limitation is reversible.

It should be performed by well-trained operators with well-maintained and calibrated equipment.30, 27

Before performing spirometry, check if the person has any contraindications (e.g. myocardial infarction, angina, aneurysm, recent surgery, suspected pulmonary embolism, suspected pneumothorax, fractured ribs). Advise them to stop if they become dizzy.

Clearly explain and physically demonstrate correct spirometry technique: 31

  • Sit upright with legs uncrossed and feet flat on the floor and do not lean forward.
  • Breathe in rapidly until lungs feel absolutely full. (Coaching is essential to do this properly.)
  • Do not pause for more than 1 second.
  • Place mouthpiece in mouth and close lips to form a tight seal.
  • Blast air out as hard and fast as possible and for as long as possible, until the lungs are completely empty or you are unable to blow out any longer.
  • Remove mouthpiece.

Repeat the test until you obtain three acceptable tests and these meet repeatability criteria.

Acceptability of test

A test is acceptable if all the following apply:

  • forced expiration started immediately after full inspiration
  • expiration started rapidly
  • maximal expiratory effort was maintained throughout the test, with no stops
  • the patient did not cough during the test
  • the patient did not stop early (before 6 seconds for adults and children over 10 years, or before 3 seconds for children under 10 years).

Record the highest FEV1 and FVC result from the three acceptable tests, even if they come from separate blows.31

Repeatability criteria

Repeatability criteria for a set of acceptable tests are met if both of the following apply:30

  • the difference between the highest and second-highest values for FEV1 is less than 150 mL
  • the difference between the highest and second-highest values for FVC is less than 150 mL.

For most people, it is not practical to make more than eight attempts to meet acceptability and repeatability criteria.31

Testing bronchodilator response (reversibility of airflow limitation)

Repeat spirometry 10-15 minutes after giving 4 separate puffs of salbutamol (100 microg/actuation) via a pressurised metered-dose inhaler and spacer.31 (For patients who have reported unacceptable side-effects with 400 microg, 2 puffs can be used.)

For adults and adolescents, record a clinically important bronchodilator response if FEV1 increases by ≥ 200 mL and ≥ 12%.31

For children, record a clinically important bronchodilator response if FEV1 increases by
≥ 12%.31

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Gastro-oesophageal reflux disease links with asthma

The majority of patients with asthma report symptoms of gastro-oesophageal reflux disease or an abnormal result on the 24-hour oesophageal pH test.32 Among children treated in referral clinics, the prevalence of gastro-oesophageal reflux disease is higher among those with asthma than those without asthma,33 but the causal link is unclear.33

Asthma may contribute to gastro-oesophageal reflux disease via changes in intrathoracic pressure or the effects of asthma medicines on the gastro-oesophageal sphincter.32

Gastro-oesophageal reflux disease may contribute to bronchoconstriction through various mechanisms (e.g. vagally mediated reflexes, increased airway hyperresponsiveness, chronic microaspiration of gastric fluid into the airways, or airway neurogenic inflammatory responses).32

Although the presence of gastro-oesophageal reflux disease is generally thought to worsen asthma control, the precise effect of gastro-oesophageal reflux disease on asthma is unclear.32

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Effects of mental illness on asthma

Psychological factors may trigger asthma symptoms and affect patients’ asthma symptom perception, but also may influence medication compliance.32

Anxiety, depression and personality disorders have been thought to be risk factors for near-fatal asthma, but the association is unclear.34 Psychological factors may trigger asthma symptoms.32 High levels of asthma-related fear and panic can exacerbate asthma symptoms.35 However, anxiety and hyperventilation attacks can also be mistaken for asthma.36

Data from a cohort study of patients with asthma attending a specialist asthma clinic suggest that comorbid generalised anxiety disorder is associated with worse asthma morbidity (poorer overall asthma control, increased bronchodilator use, and worse asthma quality of life) than patients with asthma overall.37 Several studies have reported an association between stress (socioeconomic status, interpersonal conflicts, emotional distress, terrorism) and asthma flare-ups.38 The mechanism is not yet understood, but may involve circulating adrenaline levels, altered sensitivity to corticosteroids, or mast cell activation.38

Psychological factors may influence adherence to the treatment regimen.32 The experience of euphoria or dysphoria during oral corticosteroid therapy39 may influence a person’s adherence to their written asthma action plan and could lead to delays in seeking medical care during flare-ups.

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Asthma management in obese patients

Effects of obesity on asthma control

Among people with asthma, BMI predicts asthma control, independent of airway inflammation, lung function and airway hyperresponsiveness.40

Obese people may have a reduced response to inhaled corticosteroids, compared with non-obese people.41, 42, 43  However, inhaled corticosteroids are still effective in obese people.44 Compared to people with normal BMI, people with BMI > 40 may take longer to achieve peak FEV1 after starting preventer treatment.43

There is also some evidence of a reduced response to montelukast among obese patients, but findings are not consistent.42, 43

Effects of weight loss interventions on asthma

The true effects of weight loss in people with asthma cannot be determined reliably, because many clinical trials assessing the effects of weight loss intervention on asthma have been poorly designed or reported, and have a high risk of bias.45

Systematic reviews of weight loss trials in people with asthma show that – regardless of the weight loss intervention – weight loss in people with asthma who are obese or overweight may improve asthma symptoms and reduce reliever requirement.4546 However, weight loss has not been shown to achieve clinically important improvement in lung function.45

Some recent case series studies have found that adults who underwent bariatric surgery (various procedures) were able to reduce their inhaled corticosteroid dose.4748

In an Australian clinical trial comparing a dietary intervention, an exercise intervention, and a combination of these for obese adults with asthma, asthma control improved in the diet and combination groups.49 Regardless of the method of weight loss, 5–10% weight loss was associated with a clinically important improvement in asthma control in 58% of patients, and improvement in quality of life in 83% of patients.49

In a small study in Australian children, a dietary weight loss intervention was associated with improvement in lung function, compared with baseline.50

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Upper airway dysfunction

Upper airway dysfunction is intermittent, abnormal adduction of the vocal cords during respiration, resulting in variable upper airway obstruction. It often mimics asthma5152 and is commonly misdiagnosed as asthma.3653 It can cause severe acute episodes of dyspnoea that occur either unpredictably or due to exercise.36 Inspiratory stridor associated with vocal cord dysfunction is often described as ‘wheezing’,36 but symptoms do not respond to asthma treatment.5254

Upper airway dysfunction can coexist with asthma.51 People with asthma who also have upper airway dysfunction experience more symptoms than those with asthma alone and this can result in over-treatment if vocal cord dysfunction is not identified and managed appropriately.51

Upper airway dysfunction probably has multiple causes.51 In some people it is probably due to hyperresponsiveness of the larynx in response to intrinsic and extrinsic triggers.5155 Triggers can include exercise, psychological conditions, airborne irritants, rhinosinusitis, gastro-esophageal reflux disease, and medicines.5253

Upper airway dysfunction should be considered when spirometry shows normal FEV1/FVC ratio in a patient with suspected asthma53 or symptoms do not respond to short-acting beta2 agonist reliever. The shape of the maximal respiratory flow loop obtained by spirometry may suggest the diagnosis.36 Direct observation of the vocal cords is the best method to confirm the diagnosis of upper airway dysfunction.51

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Links between allergic rhinitis and asthma

Prevalence, aetiology and symptoms

Asthma and allergic rhinitis frequently coexist. At least 75% of patients with asthma also have rhinitis, although estimates vary widely.56 Patients with asthma may have both allergic and non-allergic rhinitis.

Allergic rhinitis that starts early in life is usually due to a classical IgE hypersensitivity. Adult-onset asthma or inflammatory airway conditions typically have more complex causes. Chronic rhinosinusitis with nasal polyps is not a simple allergic condition and generally needs specialist care.57

Symptoms and signs of allergic rhinitis can be local (e.g. nasal discharge, congestion or itch), regional (e.g. effects on ears, eyes, throat or voice), and systemic (e.g. sleep disturbance and lethargy). Most people with allergic rhinitis experience nasal congestion or obstruction as the predominant symptom. Ocular symptoms (e.g. tearing and itch) in people with allergic rhinitis are usually due to coexisting allergic conjunctivitis.58

Patients may mistake symptoms of allergic rhinitis for asthma and vice versa. Allergic rhinitis is sometimes more easily recognised only after asthma has been stabilised.

Effects on asthma

Allergic rhinitis is an independent risk factor for developing asthma in children and adults.59, 60, 61, 62, 63 However, the use of antihistamines in children has not been shown to prevent them developing asthma.56

The presence of allergic rhinitis is associated with worse asthma control in children and adults.64, 65, 66, 67 The use of intranasal corticosteroids in patients with concommitant allergic rhinitis and asthma may improve asthma control in patients who are not already taking regular inhaled corticosteroids.68

Both rhinitis and asthma can be triggered by the same factors, whether allergic (e.g. house dust mite, pet allergens, pollen, cockroach) or non-specific (e.g. cold air, strong odours, environmental tobacco smoke).

Food allergies do not cause allergic rhinitis. Most people with allergic rhinitis are sensitised to multiple allergens (e.g. both pollens and house dust mite), so symptoms may be present throughout the year.

Pollens (e.g. grasses, weeds, trees) and moulds are typically seasonal allergens in southern regions, but can be perennial in tropical northern regions.69 However, ryegrass is not found in tropical regions (see Thunderstorm asthma).

Pollen calendars provide information on when airborne pollen levels are likely to be highest for particular plants.

Thunderstorm asthma

Seasonal allergic rhinitis, which in Australia is typically associated with sensitisation to perennial ryegrass (Lolium perenne), is an important risk factor for thunderstorm asthma.70

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Obstructive sleep apnoea and asthma

Links with asthma

The risk of obstructive sleep apnoea is higher among people with asthma than in the general population.71

Obstructive sleep apnoea is associated with upper and lower airway inflammation.32 Pharyngeal inflammation in obstructive sleep apnoea may promote upper airway collapse.32

Obstructive sleep apnoea syndrome is an independent risk factor for asthma flare-ups.71

In adults, unrecognised obstructive sleep apnoea may contribute to persistent asthma daytime or night-time asthma symptoms, based on cohort study evidence.7273

In obese adults, obstructive sleep apnoea may contribute to poor asthma control.74

Obstructive sleep apnoea may also interact with gastro-oesophageal reflux disease to affect asthma control in adults.74

In children, sleep-disordered breathing in children appears to be a risk factor for severe asthma, independent of obesity.75

Effects of obstructive sleep apnoea treatment on asthma

Continuous positive airway pressure (CPAP) may improve asthma in adults with concomitant obstructive sleep apnoea syndrome.76

Among children with obstructive sleep apnoea, asthma control (measured by frequency of acute asthma flare-ups, reliever use, and asthma symptoms) may improve after adenotonsillectomy.77 Tonsillectomy or adenotonsillectomy is indicated in the management of upper airway obstruction in children with obstructive sleep apnoea.78

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Comorbidity in older adults

Many older people with asthma also have multiple comorbidities and complex healthcare needs.7980 Common conditions in older people that may affect asthma control include:79

  • obesity
  • gastro-oesophageal reflux disease
  • obstructive sleep apnoea syndrome and other sleep disorders
  • osteoporosis (vertebral fractures can impair respiratory capacity)
  • cardiovascular disease (some medicines may worsen asthma).

The presence of diabetes can affect decisions about the use of systemic corticosteroids, while heart disease or anaemia can mimic symptoms.

There is limited clinical trial evidence to guide asthma management in older people with common comorbid conditions, because most asthma treatment trials have excluded people with these conditions.8179 Guidelines for one disease condition may have to be modified for older people with multiple chronic diseases to avoid potential adverse effects including drug–drug interactions.79

Common age-related problems such as cognitive impairment, poor eyesight, hearing loss, poor coordination or osteoarthritis can affect a person’s ability to use inhaler devices correctly.

Medicare items for chronic disease management (e.g. GP Management Plans, Team Care Arrangements, Multidisciplinary Care Plans) apply to patients with asthma.

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Indoor air quality

Epidemiological studies suggest that asthma symptoms are worsened by exposure to range of indoor pollutants, especially environmental tobacco smoke, fuel combustion, damp and moulds.82

Environmental tobacco smoke

Among adults with asthma, exposure to cigarette smoke (smoking or regular exposure to environmental tobacco smoke within the previous 12 months) has been associated with a significantly increased risk of needing acute asthma care within the next 2–3 years.83

Fuel combustion

Indoor exposure to nitrogen dioxide (e.g. due to gas stoves or heaters in homes, schools or workplaces) increases the risk of asthma symptoms848586 and may reduce lung function.85 Most evidence that nitrogen dioxide is an asthma trigger is from studies in children. Preventing exposure (e.g. replacing heaters with non-polluting heaters) improves symptoms of asthma and wheeze in children.87888986

Woodfire smoke can reduce lung function and increase airway inflammation in children with asthma.90 Inhaled corticosteroids may reduce the effects of wood smoke.

Damp and moulds

Several mould species have been associated with asthma, including Alternaria (e.g. Alternaria alternate), Cladosporium, Aspergillus and Penicillium.91 Two mechanisms have been reported for airway disease due to moulds: allergic sensitisation and reaction to mould aeroirritants.92

Sensitisation to Alternaria has been associated with an increased risk of hospitalisation in children with asthma.91 Epidemiological studies suggest that exposure to damp, mouldy buildings can worsen symptoms in adults and children with asthma919394 and is associated with increased risk of asthma flare-ups.

Building repairs to reduce dampness in homes (e.g. leak repair, improvement of ventilation, removal of water-damaged materials) may reduce asthma symptoms and the use of asthma medicines.95 A systematic review and meta-analysis found that damp remediation of houses reduced asthma-related symptoms including wheezing in adults, and reduced acute care visits in children.95 In children living in mouldy houses, reducing damp in the home may reduce symptoms and flare-ups, compared with cleaning advice about moulds.96

There are too few good-quality studies to conclude whether remediation of workplace buildings or schools reduces asthma symptoms.95

Antifungal medication (oral itraconazole) may improve quality of life in people with severe asthma (requiring high-dose inhaled corticosteroid treatment or frequent/continuous courses of oral corticosteroids) who are sensitised to moulds.97 However, antifungal treatment is associated with adverse effects.97

Perfumes

Asthma symptoms can be triggered by strong scents including:

There have been anecdotal reports of asthma triggered by spray deodorants.

Work-exacerbated asthma due to perfumes has also been documented.101

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Outdoor air quality

Industrial and traffic pollutants

Overall, epidemiological studies suggest that there is a strong relationship between air pollution and asthma symptoms or flare-ups, including severe acute asthma requiring hospital admission.102 Airborne pollutants associated with worsening of asthma symptoms include:103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113

  • coarse particulate matter (diameter ≤10 micrometre)
  • fine particulate matter (diameter ≤2.5 micrometre)
  • carbon monoxide
  • ozone
  • nitrogen dioxide
  • sulphur dioxide
  • diesel exhaust (multiple chemicals).

The mechanisms appear to involve airway inflammation and reduction in lung function.

Evidence from regional studies correlating recorded air pollution levels with hospital records show that pollutants from traffic sources are positively associated with emergency department visits for asthma or wheeze. Even low concentrations of ozone and traffic-related air pollutants may increase the risk of serious asthma flare-ups in children.

As little as 2 hours’ exposure to air alongside busy city roads or freeways increases airway inflammation, reduces lung function, and can cause symptoms in people with asthma.114115

Harmful effects of exposure to particulate matter are worse during warm weather.107 There may be a delay of 3–5 days between exposure to pollution and asthma flare-ups, particularly in children.106

Simultaneous exposure to pollutants (e.g. diesel exhaust, ozone) and allergens may have synergistic effects.102116 Diesel may interact with proteins to cause deposition of allergens deep in respiratory tract.102

Airborne fungi

High levels of airborne fungi (e.g. Basidiomycetes, Ascomycetes, Deuteromycetes) in urban environments were associated with increased rates of hospitalisation for asthma in a population study.116

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Allergens as asthma triggers

Allergens can trigger asthma if the person is sensitised.

Pet allergens

Contact with pets (e.g. cats, dogs and horses) can trigger asthma, mainly due to sensitisation to allergens in sebum or saliva. Exposure can trigger flare-ups or worsen symptoms.117

The amount of allergen excreted differs between breeds.117 Although some breeders claim that certain breeds of dogs that are less likely to trigger asthma (‘hypoallergenic’ breeds), allergen levels have not been shown to be lower in the animal’s hair or coat,118 or in owner’s homes119 with these breeds than other breeds.

Cat allergens easily spread on clothing and are found in places where cats have never been.117

Work-related asthma, triggered by animal urine or dander, is seen in animal workers such as breeders, jockeys, laboratory workers, pet shop workers, and people who work in veterinary surgeries.

House dust mite

Exposure to house dust mite antigens is a major asthma trigger in Australia.117

Pollens

Exposure to pollen can worsen asthma symptoms during the pollen seasons. Pollen counts are generally highest on calm, hot, sunny days in spring, early summer or during the dry season in tropical regions.

Thunderstorms are also associated with asthma flare-ups due to pollen in sensitised individuals (see: Weather events).

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Home renovation materials

Home renovation materials can trigger asthma either as sensitisers (in patients allergic to the airborne substance) or as irritants.

Home renovators may be exposed to allergens commonly responsible for work-related asthma such as wood dust (e.g. western red cedar, redwood, oak) or isocyanates in adhesives.

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Triggers in the workplace

A wide range of occupational allergens has been associated with work-related asthma. Investigation of work-related asthma is complex and typically requires specialist referral.

Table. Examples of common sensitising agents and occupations associated with exposure

Agent

Occupations

Low molecular weight agents

Wood dust (e.g. western red cedar, redwood, oak)

  • Carpenters
  • Builders
  • Model builders
  • Sawmill workers
  • Sanders

Isocyanates

  • Automotive industry workers
  • Adhesive workers
  • Chemical industry
  • Mechanics
  • Painters
  • Polyurethane foam production workers

Formaldehyde

  • Cosmetics industry
  • Embalmers
  • Foundry workers
  • Hairdressers
  • Healthcare workers
  • Laboratory workers
  • Tanners
  • Paper, plastics and rubber industry workers

Platinum salts

  • Chemists
  • Dentists
  • Electronics industry workers
  • Metallurgists
  • Photographers

High molecular weight agents

Latex

  • Food handlers
  • Healthcare workers
  • Textile industry workers
  • Toy manufacturers

Flour and grain dust

  • Bakers
  • Combine harvester drivers
  • Cooks
  • Farmers
  • Grocers
  • Pizza makers

Animal allergens (e.g. urine, dander)

  • Animal breeders
  • Animal care workers
  • Jockeys
  • Laboratory workers
  • Pet shop workers
  • Veterinary surgery workers

Source: Adapted from Hoy R, Abramson MJ, Sim MR. Work related asthma. Aust Fam Physician 2010; 39: 39-42. Available from: http://www.racgp.org.au/afp/201001/35841

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Dietary triggers

Foods are rarely a trigger for asthma.117

Food chemicals and additives

Sulphite additives (widely used as preservative and antioxidants in the food and pharmaceutical industries) have been associated with acute asthma.120

An estimated 3–10% of people with asthma are sensitised to sulphites.120

See also: Dietary salicylates

Wine

Wine has been documented to trigger asthma symptoms.121 The mechanism appears to be complex and varies between individuals.121, 122 Components of wine implicated in asthma reactions include sulphite additives and histamines.121

Although sensitivity to sulphites in wine has been demonstrated in individuals in clinical studies, this mechanism does not explain all asthmatic reactions to wine.121, 122, 123 The amount of sulphite in wine varies between brands. In general, there is more preservative in white wine than red wine, and more in cask wine than bottled wine.124

Some challenge studies suggest that antihistamines may reduce the severity of asthma symptoms due to wine.124 In general there is more histamine in red than white wines and more in Shiraz than Cabernet.124

Thermal effects

Asthma symptoms provoked by cold drinks are commonly reported anecdotally. Asthma symptoms and a reduction in FEV1 after drinking icy water have been observed in children with asthma.125 Increased bronchial hyperresponsiveness has been observed approximately 90 minutes after ingestion of ice.125

Dairy foods

Milk and other dairy foods do not increase mucus.126

Table. Association between food chemicals and asthma

Food chemical

Sources

Association with asthma

Benzoates (food additives 211, 213, 213, 216, 218)

Common preservative in soft drinks and foods

Probably minimal

Monosodium glutamate (food additive 621) and naturally occurring

Natural sources in fresh foods include tomatoes, various vegetables, mushrooms, fish, cheese, milk

Added as flavour enhancer

Probably minimal

Sulphites (food additives 221, 222, 223, 224, 225, 228)

Common preservative used in processed foods, dried fruits, medicines, beer, wine

May trigger acute asthma (uncommon)

 

Tartrazine (food additive 102)

Colouring

Probably minimal

Salicylates (naturally occurring)

Stone fruits, berries, dried fruits, gherkins, concentrated tomato products, curry powder, paprika, thyme, garam masala, rosemary, tea

Probably minimal risk for people with aspirin-exacerbated respiratory disease

Sources

Ardern K, Ram FSF. Tartrazine exclusion for allergic asthma. Cochrane Database Syst Rev 2001; Issue 4. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000460/full

Global Initiative for Asthma. Global strategy for asthma management and prevention (updated December 2012). GINA; 2012. Available from: http://www.ginasthma.org

New South Wales Food Authority. Monosodium glutamate (MSG). Publication number NSWFA/CE010/0703. Sydney: NSW Food Authority, 2013. Available from: http://www.foodauthority.nsw.gov.au

Zhou Y, Yang M, Dong BR. Monosodium glutamate avoidance for chronic asthma in adults and children. Cochrane Database Syst Rev 2012; Issue 6. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004357.pub4/full

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Aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease is a syndrome of chronic and treatment-resistant airway disease characterised by the presence of nasal polyposis, asthma, and hypersensitivity to NSAIDs, often also with eosinophilia and chronic rhinosinusitis.127

It is rare in the general population and the general asthma population, but is diagnosed in approximately 15% of patients with severe asthma and in approximately 9% of patients with chronic rhinosinusitis with nasal polyps.128

Aspirin-exacerbated respiratory disease usually develops in a person’s thirties or forties.128 If asthma develops, symptoms typically start 1–3 years after the development of rhinitis and are severe and resistant to treatment.128

The diagnosis is usually made clinically.128 A positive aspirin challenge test provides a definitive diagnosis, but the test must be conducted with extreme caution because it can provoke severe bronchospasm.128

People with aspirin-exacerbated respiratory disease may react to one or more NSAIDs.129

Montelukast may improve lung function, reduce short-acting beta2 bronchodilator use, reduce symptoms, and improve quality of life in patients with aspirin-exacerbated respiratory disease.128

People with aspirin-exacerbated respiratory disease must avoid all aspirin, including low-dose aspirin as anti-platelet therapy. They could be at risk if they use complementary medicines that contain salicylates (e.g. willowbark) or salicin (e.g. meadowsweet). COX-2 inhibitors may be a well-tolerated alternative to NSAIDs for most patients.130

Aspirin desensitisation is effective in improving asthma symptoms when provided within multidisciplinary care,131 but it must only be considered in a centre with expertise in this procedure.

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Other medicines that can trigger asthma

Beta blockers

Beta-adrenergic blocking agents (beta blockers) may cause bronchoconstriction and reduce lung function and should be used with caution in people with asthma.

Risk may be reduced with cardioselective systemic beta blockers (i.e. those that primarily block beta1-adrenergic receptors in the heart rather than beta2-receptors in the airways), such as atenolol, bisoprolol, metoprolol and nebivolol. However, selective beta blockers are not risk-free. A meta-analysis of randomised, blinded, placebo-controlled clinical trials evaluating acute beta blocker exposure in patients with asthma found hat selective beta blockers caused a fall in FEV1 of >20% in one in eight patients, and respiratory symptoms in one in 33 patients.132

Nonselective systemic beta blockers (including carvedilol, labetolol, oxprenolol, pindolol and propranolol) should not be used in people with asthma.

Ocular beta blocker preparations (e.g. timolol) may also impair respiratory function,133134 and asthma deaths have been reported.135136 Changing from timolol (nonselective) to betaxolol (selective) might improve respiratory function.134 Blocking the tear duct for 2–3 minutes after administering drops (punctual occlusion) may reduce risk of respiratory effects by minimising systemic absorption.137

Prostaglandin analogues (e.g. bimatoprost, latanoprost, travoprost), alpha2-agonists, carbonic acid inhibitors and cholinergic agents are alternative agents for managing intraocular pressure and have minimal effect on airways.133 Note that some preparations are combined with a beta blocker.

Anticholinesterases and cholinergic agents

Cholinesterase inhibitors (e.g. pyridostygmine, neostigmine, donepezil, rivastigmine, galantamine) should be used with caution in people with asthma: they may reduce lung function and theoretically could cause bronchoconstriction.

Cholinergic agents (e.g. carbachol, pilocarpine) might also cause bronchoconstriction.

Complementary medicines

Some complementary and alternative medicines may trigger asthma:

  • Echinacea138
  • bee products (pollen, propolis, royal jelly).139140141
  • complementary medicines that contain salicylates (e.g. willowbark) or salicin (e.g. meadowsweet) – could present a risk to people with aspirin-exacerbated respiratory disease
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Combination budesonide/formoterol maintenance-and-reliever regimen in adults and adolescents: overview of efficacy

Low-dose budesonide/formoterol combination can be used as reliever for asthma symptoms (instead of using a short-acting beta2 agonist reliever), in addition to its use as regular long-term preventer treatment.142, 143,  144,  145146, 147 The following formulations can be used in maintenance-and-reliever regimens:

  • dry-powder inhaler (Symbicort Turbuhaler) 100/6 microg or 200/6 microg
  • pressurised metered-dose inhaler (Symbicort Rapihaler) 50/3 microg or 100/3 microg.

Neither the 400/12 microg dry-powder inhaler nor the 200/6 microg pressurised metered-dose inhaler should be used in this way.

Overall, clinical trials show that budesonide/formoterol combination as maintenance and reliever reduces the risk of flare-ups that require oral corticosteroids, compared with other current preventer regimens and compared with a fixed higher dose of inhaled corticosteroids.148

Pooled data from five randomised controlled trials assessing budesonide/formoterol maintenance-and-reliever regimens showed that similar or better levels of asthma control were achieved with budesonide/formoterol maintenance-and-reliever compared with the conventional maintenance regimen comparators:144

  • higher-dose budesonide
  • same dose budesonide/formoterol
  • higher-dose inhaled corticosteroid/long-acting beta2 agonist (budesonide/formoterol or fluticasone propionate/salmeterol).

In randomised clinical trials in patients with a history of asthma flare-up within the previous 12 months (and therefore at greater risk of flare-up in the next 12 months), the use of formoterol/budesonide as maintenance-and-reliever regimen reduced the risk of asthma flare-ups that required treatment with oral corticosteroids, compared with the use of any of the following (plus a short-acting beta2 agonist reliever as needed):144149150

  • the same combination as maintenance treatment only
  • higher-dose combination as maintenance treatment only
  • higher-dose inhaled corticosteroids.

Meta-analysis of six randomised controlled trials found that maintenance-and-reliever treatment with budesonide/formoterol reduced the risk of severe asthma flare-ups (use of oral corticosteroids for 3 days or more, hospitalisation or emergency department visits), compared with higher-dose inhaled corticosteroid alone, or in combination with a long-acting beta2 agonist.151

In open-label studies in which patients were not selected for a previous history of flare-ups, there was no overall difference in time to first flare-up between budesonide/formoterol as maintenance-and-reliever regimen and conventional maintenance regimens (including inhaled corticosteroid or inhaled corticosteroid/long-acting beta2 agonist combinations, leukotriene receptor antagonists, xanthines or any other asthma medicines) with rapid-onset beta2 agonist reliever (selected according to clinician’s choice).152 However, the inhaled corticosteroid dose was higher with conventional maintenance regimens.

Note: The fluticasone propionate/formoterol combination is approved by the Therapeutic Goods Administration only for regular maintenance therapy.

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Inhaled corticosteroids for adults and adolescents: particle size

Medicines with small particle size CFC-free beclometasone [Qvar] and ciclesonide) achieve a greater proportion of medicine deposited in the lungs,153 and are potentially distributed more widely in the large, intermediate, and small airways.153 Although there are theoretical advantages with fine-particle formulations, including in severe asthma, the clinical implications have not been established.4

Randomised controlled trials comparing ciclesonide with fluticasone propionate in adults and adolescents have observed lower rates of patient-reported side-effects,154 and confirmed dysphonia and oral candidiasis,155 among patients using ciclesonide than among those using fluticasone propionate.

A small randomised controlled trial reported that ciclesonide treatment reduced sputum eosinophil counts in patients with refractory asthma who has previously shown persistent airway eosinophilia despite high-dose inhaled corticosteroids.156 However, this study did not provide any comparison with a higher dose of the patient’s existing inhaled corticosteroid.

Evidence from clinical trials of ciclesonide is limited. There have been no high quality double-blind studies to date, and observational studies have not been properly designed to avoid confounding factors such as prescriber bias.4

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Montelukast for adults: efficacy

In adults and adolescents with asthma that is not controlled by low-dose inhaled corticosteroid, the addition of a leukotriene receptor antagonist is less effective than the addition of a long-acting beta2 agonist in reducing the rate of asthma flare-ups that require treatment with oral corticosteroids.157 The addition of a leukotriene receptor antagonist is also associated with lesser improvement in lung function and quality of life than the addition of a long-acting beta2 agonist.157

Montelukast taken 1 hour before exercise can be used to manage exercise-induced bronchoconstriction, but it is less effective than short-acting beta2 agonists.158

Montelukast may improve lung function, reduce short-acting beta2 bronchodilator use, reduce symptoms, and improve quality of life in patients with aspirin-exacerbated respiratory disease.128

Montelukast is sometimes prescribed as add-on treatment for adults with severe asthma. Current evidence does not support its long-term use unless the patient shows a clear improvement in symptoms during a treatment trial.21

Note: PBS status as at March 2019: Montelukast treatment is not subsidised by the PBS for people aged 15 years or over. Special Authority is available for DVA gold card holders or white card holders with approval for asthma treatments.

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Tiotropium for adults and adolescents

Tiotropium via mist inhaler (not dry-powder inhaler) is approved by the TGA for add-on maintenance treatment in patients with moderate-to-severe asthma.159

Tiotropium is well tolerated.5, 160

Note: PBS status as at March 2019:

Adults: Tiotropium is subsidised by the PBS for use in combination with a maintenance combination of an inhaled corticosteroid and a long acting beta2 agonist for patients with severe asthma who have had at least one severe flare-up in the previous 12 months that required documented systemic corticosteroids, while receiving optimised asthma therapy with a combination of at least 800 mg budesonide per day or equivalent and a long acting beta2 agonist, and correct inhaler technique has been assessed, demonstrated and documented.

Children and adolescents aged 6–17 years: Tiotropium is subsidised by the PBS for use in combination with a maintenance combination of an inhaled corticosteroid and a long acting beta2 agonist for patients with severe asthma who have had at least one severe flare-up in the previous 12 months that required documented systemic corticosteroids, while receiving optimised asthma therapy with a combination of a medium-to-high dose of an inhaled corticosteroid and a long acting beta2 agonist, and correct inhaler technique has been assessed, demonstrated and documented.

Adults

Tiotropium added to inhaled corticosteroid therapy

A Cochrane review and meta-analysis that included five double-blind, double-dummy trials found that the addition of tiotropium to inhaled corticosteroid therapy reduced the risk of flare-ups requiring systemic corticosteroids and improved lung function, compared with the same dose of inhaled corticosteroid, in adults not taking a long-acting beta2 agonist.161

Another systematic review and meta-analysis of long-acting muscarinic antagonists (tiotropium or umeclidinium) in patients with poorly controlled asthma despite taking inhaled corticosteroids reported that the addition of a long-acting muscarinic antagonist significantly reduced the risk of an asthma flare-up requiring systemic corticosteroids, or of asthma worsening, compared with placebo.162 There were no significant effects on asthma control, reliever use or quality of life.162 In most included studies participants were adults with a mean age between 30 and 40 years.162

However, there is insufficient evidence overall to support the use of tiotropium as an alternative to a long-acting beta2 agonist as add-on therapy. In contrast, there is a large evidence base supporting the combination of inhaled corticosteroid and long-acting beta2 agonist in adults.

Tiotropium versus long-acting beta2 agonist added to inhaled corticosteroids

Few studies have compared tiotropium with long-acting beta2 agonists as add-on therapy in patients taking inhaled corticosteroids. Direct evidence is mainly limited to studies of less than 6 months’ duration comparing tiotropium with salmeterol. Meta-analysis of these studies showed no significant difference between treatment groups in flare-ups requiring oral corticosteroids, lung function, symptom control or asthma-related quality of life.162

While there is insufficient evidence to support the use of tiotropium as an alternative to a long-acting beta2 agonist as add-on therapy in patients taking an inhaled corticosteroid, it may be a suitable alternative for patients who have experienced adverse effects of long-acting beta2 agonist therapy.

Tiotropium added to the combination of inhaled corticosteroid and long-acting beta2 agonist

The addition of tiotropium bromide via mist inhaler therapy is effective in improving lung function and reducing worsening asthma in adults and adolescents with asthma that is uncontrolled despite taking a combination of inhaled corticosteroid and long-acting beta2 agonist, but does not reduce the rate of severe flare-ups requiring oral corticosteroid.162

A Cochrane review163 concluded that tiotropium in addition to the combination of an inhaled corticosteroid and a long-acting beta2 agonist may have additional benefits over inhaled corticosteroid/long-acting beta2 agonist alone in reducing the need for oral corticosteroids in adults with severe asthma.

Another systematic review and meta-analysis found that the addition of a long-acting muscarinic antagonist (tiotropium or umeclidinium) to the combination an inhaled corticosteroid and a long-acting beta2 agonist in adults significantly reduced the rate of worsening asthma, but not the rate of severe flare-ups requiring oral corticosteroids, and had no significant effect on other outcomes including lung function or symptom control.162

Adolescents

Tiotropium added to inhaled corticosteroid therapy

A meta-analysis of randomised placebo-controlled clinical trials in adolescents with asthma found that tiotropium as an add-on in patients taking inhaled corticosteroids improved lung function, reduced the rate of flare-ups, and improved asthma symptom control.160 In those with poorly controlled asthma despite treatment with medium-to-high doses of inhaled corticosteroids, tiotropium was not inferior to salmeterol.160

Another systematic review and meta-analysis of clinical trials of long-acting muscarinic antagonists in patients with poorly controlled asthma included only two trials evaluating tiotropium in adolescents aged 12–17 years. Tiotropium added to inhaled corticosteroid treatment was associated with numerical improvements in lung function, but this reached significance in comparison with placebo in only one study. Both studies in adolescents reported large placebo effects, which may have been due to improved adherence to inhaled corticosteroids during the trial.162

Tiotropium added to the combination of inhaled corticosteroid and long-acting beta2 agonist

A meta-analysis of randomised placebo-controlled clinical trials in adolescents with asthma reported that, among patients taking a combination of an inhaled corticosteroid and salmeterol, the addition of tiotropium increased lung function, reduced the rate of flare-ups, and improved asthma symptom control.160

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Written asthma action plans for adults

Every person with asthma should have their own written asthma action plan.

When provided with appropriate self-management education, self-monitoring and medical review, individualised written action plans consistently improve asthma health outcomes if they include two to four action points, and provide instructions for use of both inhaled corticosteroid and oral corticosteroids for treatment of flare-ups.164 Written asthma action plans are effective if based on symptoms165 or personal best peak expiratory flow (not on percentage predicted).164

How to develop and review a written asthma action plan

A written asthma action plan should include all the following:

  • a list of the person’s usual medicines (names of medicines, doses, when to take each dose) – including treatment for related conditions such as allergic rhinitis
  • clear instructions on how to change medication (including when and how to start a course of oral corticosteroids) in all the following situations:
    • when asthma is getting worse (e.g. when needing more reliever than usual, waking up with asthma, more symptoms than usual, asthma is interfering with usual activities)
    • when asthma symptoms get substantially worse (e.g. when needing reliever again within 3 hours, experiencing increasing difficulty breathing, waking often at night with asthma symptoms)
    • when peak flow falls below an agreed rate (for those monitoring peak flow each day)
    • during an asthma emergency.
  • instructions on when and how to get medical care (including contact telephone numbers)
  • the name of the person writing the action plan, and the date it was issued.

Table. Options for adjusting medicines in a written asthma action plan for adults Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/42

Table. Checklist for reviewing a written asthma action plan

  • Ask if the person (or parent) knows where their written asthma action plan is.
  • Ask if they have used their written asthma action plan because of worsening asthma.
  • Ask if the person (or parent) has had any problems using their written asthma action plan, or has any comments about whether they find it suitable and effective.
  • Check that the medication recommendations are appropriate to the person’s current treatment.
  • Check that all action points are appropriate to the person’s level of recent asthma symptom control.
  • Check that the person (or parent) understands and is satisfied with the action points.
  • If the written asthma action plan has been used because of worsening asthma more than once in the past 12 months: review the person's usual asthma treatment, adherence, inhaler technique, and exposure to avoidable trigger factors.
  • Check that the contact details for medical care and acute care are up to date.

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Templates for written asthma action plans

Templates are available from National Asthma Council Australia:

  • National Asthma Council Australia colour-coded plan, available as a printed handout that folds to wallet size and as the Asthma Buddy mobile site
  • Asthma Cycle of Care asthma action plan
  • A plan designed for patients using budesonide/formoterol combination as maintenance and reliever therapy
  • Remote Indigenous Australian Asthma Action Plan
  • Every Day Asthma Action Plan (designed for remote Indigenous Australians who do not use written English – may also be useful for others for whom written English is inappropriate).

Some written asthma action plans are available in community languages.

Software for developing electronic pictorial asthma action plans166167 is available online.

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Monoclonal antibody therapy for severe asthma

Three monoclonal antibody therapies (omalizumab, mepolizumab and benralizumab) are available in Australia for the treatment of patients with severe asthma whose asthma is uncontrolled despite optimised standard treatment including high-dose inhaled corticosteroids and long-acting beta2 agonists.

Table. Monoclonal antibody therapies currently available in Australia for severe asthma

Name Description Indication*

Dosage & route of

administration

Benralizumab (Fasenra)

Anti-IL-5 receptor

Humanised monoclonal antibody directed against IL-5 receptor Rα on surface of eosinophils and basophils

Add-on treatment for uncontrolled severe eosinophilic asthma in adults and adolescents aged ≥ 12 years

Prefilled syringe for SC injection

30 mg SC every 4 weeks for three injections then every 8 weeks
Mepolizumab (Nucala)

Anti-IL-5

Humanised monoclonal antibody directed against IL-5
Add-on treatment for uncontrolled severe eosinophilic asthma in adults and adolescents ≥12 years

Powder for SC injection in a single-use vial

100 mg SC every 4 weeks
Omalizumab (Xolair)

Anti-IgE

Humanised monoclonal antibody directed against IgE

Add-on treatment for uncontrolled severe allergic asthma in adults, adolescents and children aged ≥6 years

Prefilled syringe for SC injection

Dose calculated according to baseline IgE and body weight. Usual dose every 2–4 weeks (larger doses divided in 2 and administered every 2 weeks)

SC: subcutaneous

*Refer to TGA-approved indications and PBS criteria

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Monoclonal antibody therapy reduces the rate of severe flare-ups requiring systemic corticosteroids.[REFERENCE226], 10168, 6, 7, 15, 9, 1114, 13, 169 Many patients also experience improvement in asthma symptoms8, 10, 6, 7, 1511, 169, 170, 16 and quality of life.8, 15, 9, 12 Some studies have also shown a reduction in oral corticosteroid in patients with severe asthma.8, 10, 171, 15, 13, 169

These therapies are generally well tolerated.8, 6, 7, 14, 172 Injection site reactions are among the most common adverse events. Systemic reactions, including anaphylaxis, are rare but can occur.173

Monoclonal antibody therapies are funded by PBS only when prescribed by specialists (respiratory physician, clinical immunologist, allergist or general physician or paediatrician experienced in severe asthma management), for patients attending a public or private hospital, and when patients meet certain general and product-specific criteria. After treatment is initiated by a specialist, ongoing maintenance doses can be administered in primary care, but regular review for continuing PBS-funded treatment must be carried out by the specialist.

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Home Medicines Review and MedsCheck

Home Medicines Review

A Home Medicines Review involves the patient, their GP, an accredited pharmacist and a community pharmacy. Referral (Medicare Item 900) may be either direct to an accredited pharmacist, or to a community pharmacy that uses the services of an accredited pharmacist.

The accredited pharmacist visits the patient at their home, reviews their medicine regimen and provides a report to the person’s GP and usual community pharmacy. The GP and patient then agree on a medication management plan.

The aims of Home Medicines Review include detecting and overcoming any problems with the person’s medicines regimen, and improving the patient’s knowledge and understanding of their medicines.

Patients could be eligible for a Home Medicines Review if they (any of):

  • take more than 12 doses of medicine per day
  • have difficulty managing their own medicines because of literacy or language difficulties, or impaired eyesight
  • visit multiple specialists
  • have been discharged from hospital in the previous four weeks
  • have changed their medicines regimen during the past 3 months
  • have experienced a change in their medical condition or abilities
  • are not showing improvement in their condition despite treatment
  • have problems managing their delivery device
  • have problems taking medicines because of confusion, limited dexterity or poor eyesight.

MedsCheck

MedsCheck involves review of a patient’s medicines by a registered pharmacist within the pharmacy.

Patients are eligible if they take multiple medicines, and they do not need a referral from a GP.

The pharmacist makes a list of all the person’s medicines and medication or monitoring devices, and discusses them with the patient to identify any problems. If necessary, the pharmacist refers any issues back to the person’s GP or other health professional.

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References

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