Asthma Management Handbook

Managing allergies as part of asthma management

Recommendations

Manage allergic asthma according to the principles of asthma management in children or adults, with these considerations:

  • Identify clinically relevant allergic triggers and manage, or advise avoidance as appropriate.
  • Manage co-occurring allergic rhinitis.
  • Consider specific immunotherapy for patients who meet all the criteria.
How this recommendation was developed

Consensus

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

Consider specific allergen immunotherapy (sublingual immunotherapy or subcutaneous immunotherapy) in patients with allergic rhinitis or allergic asthma who have a history of proven, clinically important sensitisation to a particular allergen that cannot feasibly be avoided and for which for specific allergen immunotherapy is available.

Make sure the patient or parents understand that long-term treatment (at least 3 years) is necessary, and understand the cost and risks of the treatment.

Notes

Both forms of specific allergen immunotherapy require at least 3 years of treatment and should initially be prescribed by an allergy specialist (allergist or clinical immunologist) where possible. Sublingual therapy for house dust mite allergic asthma is only approved for patients who also have allergic rhinitis, and whose asthma is not well controlled with inhaled corticosteroids.

For patients with unstable asthma (e.g. frequent symptoms, marked variability in airflow measured by spirometry or peak flow monitor), the risks of treatment should be considered, and they will need specialist supervision during treatment.

How this recommendation was developed

Consensus

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

  • Australasian Society of Clinical Immunology and Allergy, 20131
  • Australasian Society of Clinical Immunology and Allergy, 19972

Omalizumab treatment can be considered for adults and adolescents aged 12 years and over, with moderate-to-severe allergic asthma despite inhaled corticosteroid treatment, and raised IgE levels.

​Note: For adults and adolescents with severe allergic asthma who may be eligible for PBS subsidy, whose asthma is not well-controlled despite optimal inhaled therapy, refer immediately for specialist assessment, because patients only become eligible for PBS subsidisation for omalizumab after at least 12 months’ care by a specialist experienced in the management of severe asthma. After treatment is established, ongoing treatment with omalizumab may be administered by a GP, with 6-monthly review of ongoing eligibility at the specialist clinic.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • Katelaris et al. 20093
  • Chung et al. 20144

Omalizumab treatment can be considered for children aged 6 to 11 years with severe allergic asthma (documented exacerbations despite daily high-dose inhaled corticosteroids with or without another maintenance treatment) and raised IgE levels.

Note: For children with severe allergic asthma who may be eligible for PBS subsidy, whose asthma is not well-controlled despite optimal inhaled therapy, refer immediately for specialist assessment, because patients only become eligible for PBS subsidisation for omalizumab after at least 6 months' care by the same specialist.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • Chung et al. 20144
  • Katelaris et al. 20093

Mepolizumab can be considered as an add-on treatment for patients aged 12 years and over with severe refractory eosinophilic asthma. Mepolizumab is given by subcutaneous injection every 4 weeks.

Note: For adults and adolescents with severe allergic asthma who may be eligible for PBS subsidy, whose asthma is not well-controlled despite optimal inhaled therapy, refer for specialist assessment, because patients only become eligible for PBS subsidisation for mepolizumab after 12 months of treatment by a specialist experienced in the management of severe asthma.

How this recommendation was developed

Consensus

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

  • Menzella et al. 20165
  • Powell et al. 20156

Consider offering referral to an allergy specialist for:

  • patients with poorly controlled asthma or allergic rhinitis, despite appropriate treatment, good adherence and good inhaler technique
  • patients considering specific immunotherapy.
How this recommendation was developed

Consensus

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

For children with allergies and family history of asthma, offer referral to a clinical immunologist or allergist for assessment for specific allergen immunotherapy.

How this recommendation was developed

Consensus

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

  • Canonica et al. 20097
  • Marogna et al. 20088
  • Novembre et al. 20049

More information

Allergies and asthma: links

There is a strong link between asthma and allergies:10, 11

  • The majority of people with asthma have allergies.
  • Immunoglobulin E-mediated sensitisation to inhalant allergens is an important risk factor for developing asthma, particularly in childhood.
  • In individuals with asthma, exposure to relevant allergens can worsen asthma symptoms and trigger flare-ups, including severe acute asthma.
  • Allergens are a common cause of occupational asthma.

Although atopic sensitisation increases the risk of developing asthma, most people who are allergic to inhalant allergens or food allergens do not have asthma.11 Among people with food allergies, asthma may be a risk factor for fatal anaphylaxis due to food allergens.1213 However, foods are rarely a trigger for asthma symtpoms.

Neither asthma nor allergy is a single disease – each has multiple phenotypes and is a complex of several different diseases with different aetiologies, genetic risk factors and environmental risk factors.10

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Allergic rhinitis and asthma: links

Prevalence, aetiology and symptoms

Asthma and allergic rhinitis frequently coexist. At least 75% of patients with asthma also have rhinitis, although estimates vary widely.14

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.15

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.16

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

Effects on asthma

The presence of allergic rhinitis is associated with worse asthma control in children and adults.17181920

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

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Allergic rhinitis and asthma: treatment

Intranasal corticosteroids

Intranasal corticosteroids are effective in reducing congestion, rhinorrhoea, sneezing and itching in adults and children with allergic rhinitis,14 and are also effective against ocular symptoms associated with allergic rhinitis.14, 21, 22 Intranasal corticosteroids are more effective in reducing nasal symptoms than other treatments,14, 21 including oral H1-antihistamines21, 23 and montelukast,14, 21 and are at least as effective as intranasal H1-antihistamines.14, 23 The use of intranasal corticosteroids in patients with concomitant allergic rhinitis and asthma may improve asthma control.2124

Intranasal corticosteroids are generally well tolerated in long-term use. In patients with asthma already taking inhaled corticosteroids, the intranasal corticosteroid dose should be taken into account when determining the total daily corticosteroid dose.

Patients need careful training to use intranasal sprays correctly. Detailed information and instructional videos for health professionals and patients are available on the National Asthma Council Australia website.

Antihistamines

Intranasal antihistamines reduce all symptoms of allergic rhinitis.23 Some have a more rapid onset of action than intranasal corticosteroids.23 Intranasal antihistamines are as effective as newer, less sedating oral H1-antihistamines,14 but are generally less effective than intranasal corticosteroids for the treatment of allergic rhinitis.21

Second-generation, less sedating oral H1-antihistamines (e.g. cetirizine, desloratadine, fexofenadine, levocetirizine or loratadine) are effective in managing allergic rhinitis symptoms of rhinorrhoea, sneezing, nasal itching and ocular symptoms,25 but are less effective for congestion.26 They are also effective for managing co-occurring ocular symptoms of allergy.21, 27

Specific allergen immunotherapy

Specific allergen immunotherapy (desensitisation) is effective in reducing allergic rhinitis symptoms (See separate topic).14, 28

Decongestants

Intranasal decongestants have a limited role in the management of allergic rhinitis because they should only be used for very short courses (up to 5 days maximum). Repeated or long-term use can cause rebound swelling of nasal mucosa necessitating dose escalation (rhinitis medicamentosa), with a risk of atrophic rhinitis.

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Specific allergen immunotherapy (desensitisation)

Options available in Australia

Two forms of specific allergen immunotherapy are available:

  • sublingual immunotherapy
  • subcutaneous immunotherapy.

Both forms of specific allergen immunotherapy require at least 3 years of treatment and should be prescribed by an allergy specialist (allergist or clinical immunologist) where possible.

Once immunotherapy has been successfully initiated by the specialist, co-management with the patient’s GP can be considered.

Commercial allergen preparations for immunotherapy are available in Australia for aeroallergens including house dust mite, pollens (e.g. grass, tree and weed pollens), animal dander and moulds.

Sublingual immunotherapy

Sublingual immunotherapy is effective in:28

  • reducing asthma symptoms in adults and children
  • reducing allergic rhinitis symptoms in adults and children
  • improving disease-specific quality of life in patients with asthma or allergic rhinitis
  • reducing medication requirements, particularly in patients allergic to grasses or house dust mite.

However, most studies have been in mild asthma, and few studies have compared immunotherapy with inhaled corticosteroid therapy, or have assessed standardised outcomes such as flare-ups.

Local adverse effects include an unpleasant taste, localised swelling in the mouth, and abdominal pain and nausea.7 Local adverse effects are common in children receiving sublingual immunotherapy.14

Anaphylaxis is extremely rare. The rate of serious systemic adverse reactions has been estimated at 1.4 serious adverse events per 100,000 doses.14728 The majority of adverse events occur soon after beginning treatment.7

The extract must be held under the tongue without swallowing for 2 minutes (liquid extracts) or 1 minute (tablets).

Asthma

Acarizax (house dust mite) is indicated for adults 18–65 years with house dust mite allergic asthma that is not well controlled by inhaled corticosteroids and is associated with mild-to-severe house dust mite allergic rhinitis.29 It is contraindicated in patients with FEV1 <70% predicted after adequate treatment, and for patients who have experienced a severe flare-up within the previous 3 months.29

Allergic rhinitis

Several commercial preparations of aeroallergens for sublingual immunotherapy in patients with allergic rhinitis are used in Australia, including:

  • Acarizax (house dust mite) – indicated for adults 18–65 years with persistent moderate to severe house dust mite allergic rhinitis despite symptomatic treatment.29
  • Actair (house dust mite) – indicated for the treatment of house dust mite allergic rhinitis with or without conjunctivitis in adults and adolescents over 12 years diagnosed with house dust mite allergy.30
  • Oralair tablets (mix of grass pollens) – indicated for adults and children over 5 years with grass pollen allergic rhinitis.31

Various single allergens and/or multiple allergen mixes are available for use as advised by the treating allergist, available as liquid extracts. Age restrictions vary between products.

Note: PBS status as at October 2016: Treatment with sublingual immunotherapy specific allergen preparations is not subsidised by the PBS.

Subcutaneous immunotherapy

Subcutaneous immunotherapy involves injections in which the dose is gradually increased at regular intervals (usually weekly), or until a therapeutic/maintenance dose is reached. This can take approximately 3–6 months.1

Subcutaneous immunotherapy is administered under medical supervision, either in a hospital or at a doctor’s office where appropriate facilities to manage potential systemic reactions are available.

Subcutaneous immunotherapy is associated with local adverse effects which may occur in up to 10% of patients (e.g. injection-site swelling) and, less frequently, serious systemic adverse effects (e.g. anaphylaxis).14, 7

Subcutaneous immunotherapy is generally not suitable for younger children (e.g. less than 7 years) because they may not be able to tolerate frequent injections.

Several commercial preparations of aeroallergens for subcutaneous immunotherapy are available in Australia, including various single allergens and/or multiple allergen mixes for use as advised by the treating allergist. Age restrictions vary between products.

Note: PBS status as at October 2016: Treatment with subcutaneous specific allergen immunotherapy preparations is not subsidised by the PBS.

 

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Omalizumab

Omalizumab is a treatment option for some adults and children aged 6 years and over with difficult-to-treat asthma.3, 4 Omalizumab is given by subcutaneous injection every 2-4 weeks.

It is approved by the Therapeutic Goods Administration for use in:32

  • adults and adolescents aged 12 years and over with moderate-to-severe allergic asthma that is not controlled while taking inhaled corticosteroid and who have raised IgE levels.
  • children aged 6 to 11 years with severe allergic asthma who have documented exacerbations despite daily high-dose inhaled corticosteroids and who have raised IgE levels.

When given in addition to inhaled corticosteroids, omalizumab is effective in helping control asthma in patients with severe asthma, particularly those with asthma that is not controlled despite regular treatment with inhaled corticosteroid at medium-to-high dose plus long-acting beta2 agonist, with or without other add-on treatments.3 Clinical trials have shown that omalizumab reduces the rate of asthma flare-ups, enables a reduction in inhaled corticosteroid dose, improves symptoms, reduces short-acting beta2 agonist reliever requirement, improves quality of life and achieves a small increase in FEV1.3

Omalizumab treatment is generally well tolerated, but is associated with injection site reactions.33 It has been associated with anaphylactoid reactions, which can occur more than 2 hours after injection,3 so patients must carry adrenaline for self-administration (e.g. EpiPen) at all times. Early reports suggested that omalizumab may be associated with an increased risk of malignancy.3 However, subsequent pooled results indicate that a causal relationship between omalizumab therapy and malignancy is unlikely.34

Note: Omalizumab treatment in adults and adolescents is subsidised through the PBS for use in patients with severe allergic asthma who meet certain criteria, including monitoring for at least 12 months by a specialist (respiratory physician, clinical immunologist, allergist or general physician) experienced in the management of patients with severe asthma. PBS criteria for continuation of treatment include demonstration of a therapeutic response by recording asthma symptom control, at baseline and after 6 months of treatment, using the 5-item Asthma Control Questionnaire (ACQ-5).

Omalizumab treatment for children aged 6 to 11 years is subsidised through the PBS for use in patients with severe allergic asthma who meet certain criteria, including monitoring for at least 6 months by a specialist (paediatric respiratory physician, clinical immunologist, or paediatrician or general physician experienced in the management of patients with severe asthma, in consultation with a respiratory physician). PBS criteria for continuation of treatment include demonstration of a therapeutic response by recording asthma symptom control, at baseline and after 6 months of treatment, using either the ACQ-5 or Asthma Control Questionnaire interviewer administered version (ACQ-IA), or reduction in time-adjusted exacerbation rates compared with the 12 months before treatment.

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Mepolizumab

Mepolizumab is a biological humanised anti-interleukin-5 (IL-5) monoclonal antibody (human IgG1) which reduces the number of eosinophils in sputum and blood. It is indicated for add-on treatment of severe refractory eosinophilic asthma in patients aged 12 years or over and is administered by subcutaneous injection once every 4 weeks.35

In people with severe eosinophilic asthma, mepolizumab treatment has been shown to reduce the rate of asthma flare-ups, improve health-related quality of life, and reduce the need for systemic corticosteroids.6, 5, 36

Adverse effects include hypersensitivity reactions such as urticaria, angioedema, rash, bronchospasm, hypotension. These generally occur within hours of administration, but reactions up to days after administration have been recorded.35 No cases of anaphylaxis were recorded in a 52-week open-label study of subcutaneous mepolizumab, conducted among patients who had participated in two randomised controlled trials.37

Note: Mepolizumab treatment in adults and adolescents is subsidised through the PBS for use in patients with severe allergic asthma who meet certain criteria, including treatment by a specialist (respiratory physician, clinical immunologist, allergist or general physician) experienced in the management of patients with severe asthma. PBS criteria for continuation of treatment include demonstration of a therapeutic response by recording asthma symptom control, at base line and after 6 months of treatment, using the 5-item Asthma Control Questionnaire (ACQ-5).

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References

  1. Australasian Society of Clinical Immunology and Allergy (ASCIA). Allergen Immunotherapy. ASCIA, Sydney, 2013. Available from: http://www.allergy.org.au/patients/allergy-treatment/immunotherapy
  2. Australasian Society of Clinical Immunology and Allergy. Specific allergen immunotherapy for asthma. A position paper of the Thoracic Society of Australia and New Zealand and the Australasian Society of Clinical Immunology and Allergy. Med J Aust. 1997; 167: 540-4. Available from: https://www.mja.com.au/journal/1997/167/10/specific-allergen-immunotherapy-asthma
  3. Katelaris CH, Douglass J, Gibson PG, et al. Omalizumab. Recommendations for use in the Australasian context (A consensus paper of the Thoracic Society of Australia and New Zealand). Thoracic Society of Australia and New Zealand, 2009. Available from: http://www.thoracic.org.au/professional-information/position-papers-guidelines/asthma/
  4. Chung, K. F., Wenzel, S. E., Brozek, J. L., et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. The European respiratory journal. 2014; 43: 343-73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24337046
  5. Menzella, F., Lusuardi, M., Montanari, G., et al. Clinical usefulness of mepolizumab in severe eosinophilic asthma. Therapeutics and clinical risk management. 2016; 12: 907-16. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27354806
  6. Powell, Colin, Milan, Stephen J., Dwan, Kerry, et al. Mepolizumab versus placebo for asthma. **. 2015; : . Available from: http://dx.doi.org/10.1002/14651858.CD010834.pub2
  7. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy. World Allergy Organization information position paper 2009. WAO Journal. 2009; November: 233-281. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488881/
  8. Marogna M, Tomassetti D, Bernasconi A, et al. Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study. Ann Allergy Asthma Immunol. 2008; 101: 206-211. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18727478
  9. Novembre E, Galli E, Landi F, et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2004; 114: 851-857. Available from: http://www.jacionline.org/article/S0091-6749(04)02008-1/fulltext
  10. National Asthma Council Australia. Asthma and allergy. National Asthma Council Australia, Melbourne, 2012. Available from: http://www.nationalasthma.org.au/publication/asthma-allergy-hp
  11. Custovic A, Simpson A. The role of inhalant allergens in allergic airways disease. J Investig Allergol Clin Immunol. 2012; 22: 393-401. Available from: http://www.jiaci.org/issues/vol22issue6/vol22issue06-1.htm
  12. Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001; 107: 191-3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11150011
  13. Bock SA, Muñoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol. 2007; 119: 1016-1018. Available from: http://www.jacionline.org/article/S0091-6749(06)03814-0/fulltext
  14. Brożek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision. J Allergy Clin Immunol. 2010; 126: 466-476. Available from: http://www.jacionline.org/article/S0091-6749(10)01057-2/fulltext
  15. National Asthma Council Australia. Managing allergic rhinitis in people with asthma. An information paper for health professionals. National Asthma Council Australia, Melbourne, 2012. Available from: http://www.nationalasthma.org.au/publication/allergic-rhinitis-asthma-hp
  16. Spangler DL, Abelson MB, Ober A, Gotnes PJ. Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models. Clin Ther. 2003; 25: 2245-67. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14512132
  17. Pawankar R, Bunnag C, Chen Y, et al. Allergic rhinitis and its impact on asthma update (ARIA 2008)–western and Asian-Pacific perspective. Asian Pac J Allergy Immunol. 2009; 27: 237-243. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20232579
  18. de Groot EP, Nijkamp A, Duiverman EJ, Brand PL. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax. 2012; 67: 582-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22213738
  19. Thomas M, Kocevar VS, Zhang Q, et al. Asthma-related health care resource use among asthmatic children with and without concomitant allergic rhinitis. Pediatrics. 2005; 115: 129-34. Available from: http://pediatrics.aappublications.org/content/115/1/129.long
  20. Price D, Zhang Q, Kocevar VS, et al. Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults. Clin Exp Allergy. 2005; 35: 282-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15784104
  21. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: An updated practice parameter. J Allergy Clin Immunol. 2008; 122: S1-S84. Available from: http://www.jacionline.org/article/S0091-6749(08)01123-8/fulltext
  22. Hong J, Bielory B, Rosenberg JL, Bielory L. Efficacy of intranasal corticosteroids for the ocular symptoms of allergic rhinitis: A systematic review. Allergy Asthma Proc. 2011; 32: 22-35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21262095
  23. Kaliner MA, Berger WE, Ratner PH, Siegel CJ. The efficacy of intranasal antihistamines in the treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2011; 106: S6-s11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21277531
  24. Kersten ET, van Leeuwen JC, Brand PL, et al. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children. Pediatr Pulmonol. 2012; 47: 27-35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22170807
  25. Bachert C, Maspero J. Efficacy of second-generation antihistamines in patients with allergic rhinitis and comorbid asthma. J Asthma. 2011; 48: 965-73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21970671
  26. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008. Allergy. 2008; 63: 8-160. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2007.01620.x/full
  27. Howarth PH. Assessment of antihistamine efficacy and potency. Clin Exp Allergy. 1999; 29 Suppl 3: 87-97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10444220
  28. Lin S, Erekosima N, Kim J, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: A systematic review. JAMA. 2013; 309: 1278-1288. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23532243
  29. Seqirus. Product Information: Acarizax (standardised allergen extract from the house dust mites. Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  30. Stallergenes. Product Information: Actair Initiation Sublingual Tablets 100 IR & 300 IR and Actair Continuation Treatment Sublingual Tablets 300 IR (mixture of. Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  31. Stallergenes. Product Information: Oralair (allergen pollen extract of five grasses). Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  32. Novartis Pharmaceuticals Australia Pty Ltd. Product Information: Xolair (omalizumab). Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  33. Walker S, Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev. 2006; Issue 2: CD003559. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003559.pub3/full
  34. Busse W, Buhl R, Fernandez Vidaurre C, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol. 2012; 129: 983-9.e6. Available from: http://www.jacionline.org/article/S0091-6749(12)00069-3/fulltext
  35. GlaxoSmithKline Australia Pty, Ltd. Product Information: Nucala (mepolizumab). Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  36. Bel, E. H., Wenzel, S. E., Thompson, P. J., et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. The New England journal of medicine. 2014; 371: 1189-97. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25199060
  37. Lugogo, N., Domingo, C., Chanez, P., et al. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. Clinical therapeutics. 2016; 38: 2058-2070.e1. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27553751