Asthma Management Handbook

Considering the patient’s general health during asthma management


Recommendations

Manage allergies, including allergic rhinitis.

How this recommendation was developed

Adapted from existing guidance

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

  • National Asthma Council Australia, 20121

Identify and manage other comorbid conditions that can affect asthma or contribute to respiratory symptoms (e.g. chronic obstructive pulmonary disease, gastro-oesophageal reflux disease, obstructive sleep apnoea syndrome, obesity, mental illness).

How this recommendation was developed

Consensus

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

In patients with moderate-to-severe asthma or asthma that is difficult to control, screen for depression, panic disorder and anxiety disorder, and offer comprehensive assessment, treatment or referral as appropriate.

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):

  • Alvarez and Fitzgerald, 20072
  • Boulet, 20093
  • Lavoie et al. 20114
  • Parry et al. 20125
  • Theoharides et al. 20126
  • Weinberger and Abu-Hasan, 20077

For patients who are interested in using complementary therapies, discuss expectations and provide information about safety and efficacy.

How this recommendation was developed

Consensus

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

More information

Treatment of allergic rhinitis in adults and adolescents

 

Table. Overview of efficacy of allergic rhinitis medicines for specific symptoms Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/102

Intranasal corticosteroids

If continuous treatment is required, an intranasal corticosteroid is the first-choice treatment unless contraindicated. Intranasal corticosteroids are more effective in the treatment of allergic rhinitis than other drug classes including oral H1-antihistamines, intranasal H1-antihistamines and montelukast.8, 9, 10 Intranasal corticosteroid are most effective when taken continuously.8

Intranasal corticosteroids are effective in reducing congestion, rhinorrhoea, sneezing and itching in adults and adolescents with allergic rhinitis.8, 9 They are also effective for ocular symptoms.11

All available intranasal corticosteroids appear to be equally effective.8

The onset of action is between 3 and 36 hours after first dose and, in practice, the full therapeutic effect takes a few days.12

The addition of an oral H1-antihistamine or leukotriene receptor antagonist to an intranasal corticosteroid is generally no more effective than intranasal corticosteroid monotherapy.10

Intranasal corticosteroids are well tolerated. Common (>1%) adverse effects include nasal stinging, itching, nosebleed, sneezing, sore throat, dry mouth, cough.13 Nose bleeds are usually due to poor spray technique or crusting. Evidence from studies mainly in adults suggests that intranasal corticosteroids do not cause atrophy of nasal epithelium.14

Intranasal corticosteroids are not generally associated with clinically significant systemic adverse effects when given in recommended doses.8, 15 Studies in adults evaluating effects on the hypothalamic-pituitary axis using morning cortisol concentrations, cosyntropin stimulation, and 24-hour urinary free cortisol excretion show no adverse effects with beclomethasone dipropionate, budesonide, ciclesonide, fluticasone propionate, fluticasone furoate, or triamcinolone acetonide.8

In patients with asthma already taking inhaled corticosteroids, both the intranasal corticosteroid dose and the inhaled corticosteroid dose should be taken into account when calculating the total daily corticosteroid dose. Drug–drug interactions (e.g. with CYP3A4 inhibitors such as such as erythromycin, clarithromycin, ritonavir and itraconazole) may change the metabolism or increase absorption of corticosteroids administered by any route, increasing the risk of adrenal suppression.13

Combination intranasal corticosteroid plus intranasal antihistamines

Combined intranasal fluticasone propionate and azelastine hydrochloride in a single device is more effective than fluticasone propionate alone for a range of nasal and ocular symptoms.8, 10, 16

The onset of therapeutic action is approximately 30 minutes after dosing.16

Oral antihistamines

Second-generation (less sedating) antihistamines (e.g. cetirizine, desloratadine, fexofenadine or loratadine) should be used in preference to older, more sedating antihistamines. Cetirizine is the most likely of the less sedating antihistamines to cause sedation, while fexofenadine and loratadine appear to be the least sedating.17

Less sedating oral H1-antihistamines are effective in managing allergic rhinitis symptoms of rhinorrhoea, sneezing, nasal itching and ocular symptoms.10, 18 They can provide adequate relief for some individuals when taken continuously or intermittently.8 Available agents appear to be equally effective.15

However, oral antihistamines are less effective than continuous intranasal corticosteroids, especially for nasal congestion.8, 19 In adults with allergic rhinitis, oral antihistamines usually produce no further improvement when added to intranasal corticosteroid treatment.8

Common (>1%) adverse effects include drowsiness, fatigue, headache, nausea and dry mouth.13 Oral antihistamines can also cause ocular dryness.20

Intranasal antihistamines

Intranasal antihistamines are at least equally effective as second-generation, less sedating oral H1-antihistamines for the treatment of allergic rhinitis, but are generally less effective than intranasal corticosteroids.9

Intranasal antihistamines are more effective than oral antihistamines for reducing nasal congestion.8 They have a rapid onset of action (15–30 minutes).8

The most common (>1%) adverse effect is local irritation.13 Bitter taste is more common intranasal antihistamines than with intranasal corticosteroids.8

Montelukast

Leukotriene receptor antagonists are no more effective than oral H1-antihistamines.9, 10 Montelukast is less effective than intranasal corticosteroid in the treatment of allergic rhinitis.8, 9 In most studies, adding montelukast to an intranasal corticosteroid was not more effective than intranasal corticosteroid alone.10

Montelukast is approved by TGA for treatment of in adults with asthma or seasonal allergic rhinitis.

It is generally very well tolerated, but has been infrequently associated with neuropsychiatric adverse effects, including suicidal ideation, in children and young people.21, 22, 23, 24, 25 A recent analysis of databases of adults and children taking montelukast suggests it is associated with nightmares, depression, and aggression.25 Allergic granulomatous angiitis has also been reported, but a causal relationship has not been established.25

Other nasal sprays

Ipratropium bromide spray is effective in managing persistent rhinorrhoea in patients with allergic rhinitis, but not blockage or itch.9 It is indicated for use in adults and adolescents over 12 years old.

Intranasal sodium cromoglycate is less effective than intranasal corticosteroids, but is effective in some patients for prevention and treatment of allergic rhinitis and is associated with minimal adverse effects.15

Specific allergen immunotherapy

Specific allergen immunotherapy (desensitisation) is effective in reducing allergic rhinitis symptoms (see separate topic).

Last reviewed version 2.0

Close
Treatment of allergic rhinitis in children

 

Table. Overview of efficacy of allergic rhinitis medicines for specific symptoms Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/102

Intranasal corticosteroids

Intranasal corticosteroids are effective in reducing congestion, rhinorrhoea, sneezing and itching in school-aged children with allergic rhinitis.8, 9 However, there is weaker evidence to support their efficacy in children than in adults.9 There is limited evidence to guide the treatment of allergic rhinitis in preschool children.10

The addition of an oral H1-antihistamine or leukotriene receptor antagonist to an intranasal corticosteroid is generally no more effective than intranasal corticosteroid monotherapy.10

TGA-approved indications vary between age groups. Intranasal corticosteroids indicated for children aged under 12 years include fluticasone furoate (age 2 years and over), mometasone furoate (age 3 years and over), and budesonide (age 6 years and over).

Intranasal corticosteroids are well tolerated. Evidence from studies mainly in adults suggests that they do not cause atrophy of nasal epithelium.26 Intranasal corticosteroids are not generally associated with clinically significant systemic adverse effects in children when given in recommended doses.815 Studies in children evaluating effects on the hypothalamic-pituitary axis using morning cortisol concentrations, cosyntropin stimulation, and 24-hour urinary free cortisol excretion showed no adverse effects with ciclesonide, fluticasone propionate, fluticasone furoate, mometasone furoate, or triamcinolone acetonide.8 One knemometry study showed reduced lower leg growth rate in children using intranasal budesonide.8 In studies using stadiometry over 12 months, higher-than-recommended doses of intranasal beclomethasone dipropionate were associated with growth suppression, but fluticasone propionate and mometasone furoate showed no effects on growth compared with placebo.8

In children already taking inhaled corticosteroids, both the intranasal corticosteroid dose and the inhaled corticosteroid dose should be taken into account when calculating the total daily corticosteroid dose.

Oral antihistamines

Second-generation (less sedating) antihistamines (e.g. cetirizine, desloratadine, fexofenadine or loratadine) should be used in preference to older, more sedating antihistamines. Cetirizine is the most likely of the less sedating antihistamines to cause sedation, while fexofenadine and loratadine appear to be the least sedating.17

These antihistamines can be taken long term by children. Eighteen months of treatment with cetirizine was well tolerated in a large, prospective, multi-country, randomised controlled trial in infants with atopic dermatitis aged 12–24 months.27

Less sedating oral H1-antihistamines are effective in managing allergic rhinitis symptoms of rhinorrhoea, sneezing, nasal itching and ocular symptoms,10, 18 including in preschool children. 10 They can provide adequate relief for some individuals when taken continuously or intermittently.8 Available agents appear to be equally effective.15

However, oral antihistamines are less effective than continuous intranasal corticosteroids, especially for nasal congestion.8, 19 The addition of oral antihistamines to intranasal corticosteroids has not been demonstrated to be an effective strategy in children.28

TGA-approved indications vary between age groups. Less sedating oral antihistamines indicated for children under 12 years include cetirizine (1 year and over), loratatidine (1 year and over), desloratadine (6 months and over), and fexofenadine (6 months and over).

Intranasal antihistamines

Intranasal antihistamines are at least equally effective as second-generation, less sedating oral H1-antihistamines for the treatment of allergic rhinitis, but are generally less effective than intranasal corticosteroids.9

Intranasal antihistamines are more effective than oral antihistamines for reducing nasal congestion.8 They have a rapid onset of action (15–30 minutes).8

Montelukast

Leukotriene receptor antagonists are no more effective than oral H1-antihistamines.9, 10 Montelukast is less effective than intranasal corticosteroid in the treatment of allergic rhinitis.8, 9 In most studies, adding montelukast to an intranasal corticosteroid was not more effective than intranasal corticosteroid alone.10

Montelukast is approved by TGA for the treatment of asthma in children over 2 years, and for the treatment of seasonal allergic rhinitis.

It is generally very well tolerated, but has been infrequently associated with neuropsychiatric adverse effects, including suicidal ideation, in children and young people.21, 22, 23, 24 A recent analysis of databases of adults and children taking montelukast suggests it is associated with nightmares (especially in children), depression, and aggression (especially in children).25 Allergic granulomatous angiitis has also been reported, but a causal relationship has not been established.25

The potential association of montelukast with behaviour-related adverse events should be mentioned to parents when commencing treatment, and treatment should be stopped if such adverse events are suspected.

Specific allergen immunotherapy

Specific allergen immunotherapy (desensitisation) is effective in reducing allergic rhinitis symptoms (see separate topic).

Last reviewed version 2.0

Close
Non-recommended medications for allergic rhinitis

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 (rhinitis medicamentosa), which can lead to dose escalation by patients, with a risk of atrophic rhinitis. Intranasal decongestants can be considered for a patient with severe nasal congestion to gain rapid relief of symptoms until the full effect of intranasal corticosteroids is achieved.

Oral decongestants (e.g. pseudoephedrine or phenylephrine) should not generally be used in the management of allergic rhinitis. They are indicated for short-term use only (e.g. acute infectious rhinitis, or during air travel by a patient with symptomatic rhinitis, as a single tablet taken one hour before landing). They are associated with adverse effects including palpitations, tachycardia and insomnia.

Oral corticosteroids should be avoided as a treatment for allergic rhinitis. In exceptional circumstances, their use might be considered in consultation with an allergy specialist.

Topical ocular alpha agonist vasoconstrictors (including in combination with antihistamines) should not be used for allergic conjunctivitis because they can cause conjunctivitis medicamentosa.

Close
Nasal saline irrigation for allergic rhinitis

Nasal irrigation (via a syringe, rinse bottle, spray or other device) can improve nasal symptoms, mucociliary clearance, and quality of life.29 Saline administered by spray or other devices was used at least twice daily in most studies that showed a benefit.29

Isotonic solution is preferable to hypertonic solution because it supports optimal mucociliary clearance.29 Isotonic saline is solution is inexpensive and has no known adverse effects.29 Patients can use either commercially manufactured saline solutions or home-made normal saline: 1 teaspoon (5 g) rock or sea salt in 500 mL of water (preferably bottled or boiled).

There is not enough evidence to determine:

  • whether solutions should be buffered or non-buffered, sterile or non-sterile
  • whether various additives provide any advantage
  • whether inhaling steam or an irritant decongestant (e.g. eucalyptus, menthol) before saline irrigation provides any extra benefit. However, patients are more likely to adhere to simple and convenient regimens, regardless of theoretical advantages. Caution is required with steam inhalation to avoid burns.

If patients are using both saline irrigation and an intranasal corticosteroid or intranasal H1‑antihistamine, they should perform saline irrigation first. Saline can be used again after waiting at least an hour after using an intranasal corticosteroid.

Young children are unlikely to tolerate nasal irrigation.

Close
Surgical turbinate reduction

Turbinate reduction surgery can be considered when nasal obstruction is due to turbinate hypertrophy and symptoms do not respond to medical treatment. It should not be performed in young children except after thorough investigation and review.

Inferior turbinate hypertrophy secondary to inflammation is a common cause of nasal obstruction in patients with allergic rhinitis.30 Several surgical procedures are available to correct this problem.31 The ideal surgical reduction should preserve the mucosa and physiological function.30

Short-term adverse outcomes of inferior turbinate reduction include nasal bleeding, scarring and crusting. Rarely, it may worsen symptoms when patients have non-specific rhinitic conditions or sino-nasal somatisation disorders (‘empty nose syndrome’).31 There is no evidence that turbinate surgery creates these conditions, but sino-nasal surgery may exacerbate the symptoms.

 

Close
Specific allergen immunotherapy (desensitisation)
  • Specific allergen immunotherapy should not be started unless the patient has stable asthma, including spirometry-demonstrated forced expiratory volume in 1 second (FEV1) greater than 80% predicted for subcutaneous immunotherapy and greater than 70% predicted for sublingual immunotherapy.32, 33 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. These patients will need specialist supervision during treatment.

Options available in Australia

Two forms of specific allergen immunotherapy are available:

  • sublingual immunotherapy
  • subcutaneous immunotherapy.

Both forms of specific allergen immunotherapy require 3–5 years of treatment. Specific allergy immunotherapy can be repeated.

Although some specific allergen therapies can be prescribed by primary care health professionals, it is recommended that they are initiated under the care of an allergy specialist (allergist or clinical immunologist), where possible.

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.

Overview of efficacy

There is strong evidence that allergen immunotherapy is effective in the treatment of seasonal and perennial allergic rhinitis.34, 35, 10 There is less evidence supporting specific allergen immunotherapy in children than in adults.35 Specific allergen immunotherapy in children with seasonal allergic rhinoconjunctivitis might prevent development of asthma.36, 37, 38

Single-allergen specific allergen immunotherapy is effective in patients sensitised to one allergen and those sensitised to multiple allergens.39, 40, 41 In selected cases more than one allergen may be administered as separate extracts. There is weak evidence for the efficacy of allergen mixes.42

A systematic review of studies directly comparing subcutaneous immunotherapy and sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma found:43

  • low-grade evidence that subcutaneous immunotherapy is more effective than sublingual immunotherapy for reducing asthma symptoms and for reducing a combined measure of rhinitis symptoms and medication use
  • moderate-grade evidence that subcutaneous immunotherapy is more effective than sublingual immunotherapy for reducing nasal and/or eye symptoms.

Sublingual immunotherapy is associated with a lower rate of severe adverse effects (anaphylaxis and death) than subcutaneous immunotherapy, based on indirect comparison.9, 44, 45

Sublingual immunotherapy

Sublingual immunotherapy (self-administered at home) is effective for the treatment of allergic rhinitis in adults and children.46, 47 The greatest benefits have been demonstrated in those with allergies to temperate grass pollens or house dust mite.47 Therapeutic Goods Administration (TGA)-approved indications for commercially available preparations vary according to age group.

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

Sublingual immunotherapy is generally well tolerated.46 Local adverse effects are common in children receiving sublingual immunotherapy.9 Systemic adverse reactions, such as anaphylaxis, are very rare.9 The majority of adverse events occur soon after beginning treatment.47

TGA-approved indications

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.48 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.48

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.48
  • 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.49
  • Grazax (Timothy grass [Phleum pratense] pollen extract) – indicated for adults, adolescents and children older than 5 years with allergic rhinitis induced by Timothy grass50
  • Oralair tablets (mix of grass pollens) – indicated for adults and children over 5 years with grass pollen allergic rhinitis.51

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.52 Treatment is then continued for a further 3–5 years.

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.

Subcutaneous immunotherapy is effective for the treatment of allergic rhinitis and asthma, particularly when single-allergen immunotherapy regimens are used.44 There is strong evidence that it reduces asthma symptoms, asthma medication usage, rhinitis/rhinoconjunctivitis symptoms, conjunctivitis symptoms, and rhinitis/rhinoconjunctivitis disease-specific quality of life, in comparison to placebo or usual care.44 There is also moderate evidence that subcutaneous immunotherapy reduces rhinitis/rhinoconjunctivitis medication usage.44

Subcutaneous immunotherapy is associated with local adverse effects (e.g. injection-site swelling) and, less frequently, serious systemic adverse effects.9, 47 The most common systemic reactions are respiratory symtoms. There have been few reports of anaphylaxis.9

Note: PBS status as at March 2019: Treatment with subcutaneous specific allergen immunotherapy preparations is not subsidised by the PBS.

Last reviewed version 2.0

Close
Asthma–COPD overlap

Distinguishing between typical allergic asthma (childhood-onset allergic asthma) and typical COPD (emphysema in a heavy smoker) is straightforward.53 However, it can be difficult to distinguish COPD from asthma in adults who have features of both conditions.54, 55These people are described as having asthma–COPD overlap.54, 53, 56

Asthma–COPD overlap is not a single, well-defined disease entity, but includes a range of airway disease phenotypes with different causal mechanisms.54, 57 Features of both asthma and COPD have been described in:56, 58, 59, 60

  • people with current asthma (allergic or non-allergic) who have had significant exposure to tobacco smoke
  • people with longstanding asthma or late-onset asthma who have become persistently short of breath over time
  • people significant smoking history and symptoms consistent with COPD who also have a history of childhood asthma
  • people who present in middle age or later with shortness of breath, with a history of childhood asthma but no or few symptoms in between, and little smoking history.

Figure. Development of asthma, COPD and asthma–COPD overlap Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/figure/show/108

People with asthma–COPD overlap often have poor disease outcomes, including:54, 6162, 63, 64

  • high need for healthcare services
  • worse quality of life, more wheezing, dyspnoea, cough and sputum production, and more frequent and severe respiratory exacerbations and hospitalisations, than people with COPD or asthma alone
  • worse lung function demonstrated by spirometry than those with COPD alone, despite lower average exposure to tobacco smoke.

Features of asthma, COPD and asthma–COPD overlap

If several features of both asthma and COPD are present and neither condition is strongly favoured, respiratory disease should be managed according to recommendations for asthma–COPD overlap.

Table. Features that, when present, favour asthma or COPD

Clinical feature (if measured/relevant)

Asthma more likely

COPD more likely

Age of onset

Before 20 After 40

Pattern of symptoms

Variation in respiratory symptoms:

  • changes over minutes, hours or days
  • worse at night or early morning
  • triggered by exercise, emotions, airborne pollutants or allergens

Persistence of respiratory symptoms despite treatment

Symptoms every day, including exertional dyspnoea

History of chronic cough and sputum unrelated to specific triggers, before onset of dyspnoea

Lung function

Expiratory airflow limitation* is variable#

Lung function normal between symptoms

Expiratory airflow limitation* is persistent

Lung function abnormal between symptoms

History

Previous diagnosis of asthma

Family history of asthma and allergies§ (allergic rhinitis or eczema)

Previous diagnosis of COPD, chronic bronchitis or emphysema

Heavy exposure to tobacco smoke or biomass fuels

Long-term disease trajectory

Seasonal or yearly variation in symptoms

Improvements (spontaneously or in response to medication) last for weeks

Slowly worsens over years

Relief in response to medication is limited and short term

Chest X-ray

Normal Severe hyperinflation

Features that, when present, increase the probability of either typical asthma or typical COPD. None of these features is essential to make the diagnosis of asthma or COPD, with the exception of persistent airflow limitation for making the diagnosis of COPD.

* Expiratory airflow limitation: indicated by a reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) on spirometry (FEV1/FVC less than the lower limit of normal (i.e. less than the 5th percentile of normal population). Typical FEV1/FVC values derived from population studies are > 0.75 in people aged 40–59 years and > 0.70 in people aged 60–80 years.

# Variable expiratory airflow limitation: variation beyond the range seen in healthy populations. It is indicated in adults by any of the following:

  • a clinically important increase in FEV1 (change in FEV1 of at least 200 mL and 12% from baseline) 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 increase in lung function (at least 200 mL and 12% from baseline) after ≥ 4 weeks’ treatment trial with an ICS
  • clinically important variation in peak expiratory flow (diurnal variability of more than 10%, calculated over 1–2 weeks as the average of daily amplitude per cent mean)
  • 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 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.

The greater the variations, or the more occasions excess variation is seen, the more confidently the diagnosis of variable expiratory airflow limitation consistent with asthma can be made.

† Persistent expiratory airflow limitation is indicated by reduced post-bronchodilator FEV1/FVC*

§ Lack of history of atopy does not exclude non-allergic asthma.

‡ Chest X-ray may be normal in a patient with COPD

Adapted from

Global Initiative for Asthma, Global Initiative for Obstructive Lung Disease. Diagnosis and initial treatment of asthma, COPD and asthma-COPD overlap. Updated April 2017. Global Initiative for Asthma and Global Initiative for Obstructive Lung Disease; 2017. Available from: http://ginasthma.org/gina-reports

Asset ID: 104

Close

Table. Spirometry findings in asthma, COPD and asthma–COPD overlap

Finding

Consistent with

Asthma COPD Asthma–COPD overlap

Normal FEV1 /FVC before of after bronchodilator

  Yes   No   No *

Abnormal lung function

(post-bronchodilator reduced FEV1/FVC and FEV1 < lower limit of normal)

  Yes #   Yes   Yes

Airflow limitation with greater bronchodilator reversibility than in healthy population

(post-bronchodilator FEV1 increase ≥ 12% and 200mL from baseline)

  Yes   Yes   Yes

Marked bronchodilator reversibility

(FEV1 increase ≥ 12% and 400mL from baseline)

  Yes   Possible but unusual   Possible §

FEV1/FVC: ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC), either before or after bronchodilator

* Normal FEV1/FVC is not consistent with COPD unless there is other evidence of chronic non-reversible expiratory airflow limitation.

# This finding is consistent with asthma that is poorly controlled or measured during a flare-up, or can be seen in some patients with longstanding asthma.

‡ The greater the variation, and the more times variation is seen, the more likely the diagnosis of asthma. However, some patients with longstanding asthma may develop persistent airflow limitation.

† Marked reversibility strongly favours asthma and is generally inconsistent with COPD, but does not rule out asthma–COPD overlap.

§ This finding may be seen in patients with asthma–COPD overlap, or occasionally in COPD, especially when FEV1 is low.

Sources

Global Initiative for Asthma, Global Initiative for Obstructive Lung Disease. Diagnosis and initial treatment of asthma, COPD and asthma-COPD overlap. Updated April 2017. Global Initiative for Asthma and Global Initiative for Obstructive Lung Disease; 2017. Available from: http://ginasthma.org/gina-reports

Woodruff P, van den Berge M, Boucher R et al. ATS-NHLBI Asthma COPD Overlap (ACO) Workshop Report. Am J Respir Crit Care Med 2017; 196:375-381. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28636425

 

Asset ID: 103

Close

Treatment for patients with asthma–COPD overlap

Inhaled corticosteroid treatment at low–moderate doses is essential to reduce the risk of potentially life-threatening flare-ups, even if asthma symptoms appear mild or infrequent.54, 65

Most patients also need treatment with a long-acting bronchodilator (either long-acting beta2 agonist or long-acting muscarinic antagonist) in addition to an inhaled corticosteroid. Long-acting beta2 agonists and long-acting muscarinic antagonists should not be used by people with asthma or asthma–COPD overlap unless they are also taking an inhaled corticosteroid (either in combination or separately).

Table. Long-acting bronchodilators for asthma–COPD overlap

Class

Dosing frequency

Agent

Brand name

ICS–LABA combinations

Once daily

Fluticasone furoate + vilanterol

Breo Ellipta 100/25 microg

  • Do not prescribe 200/25 microg formulation#
Twice daily

Budesonide + formoterol

Symbicort Rapihaler

Symbicort Turbuhaler

Twice daily

Fluticasone propionate + formoterol

Flutiform

Twice daily

Fluticasone propionate + salmeterol

Fluticasone and Salmeterol Cipla

Seretide Accuhaler

Seretide MDI

LABAs*

Once daily

Indacaterol

Onbrez Breezhaler

Twice daily Formoterol

Oxis

Foradile

Twice daily Salmeterol

Serevent Accuhaler

LAMAs* Once daily Glycopyrronium

Seebri Breezhaler

Once daily

Tiotropium

Spiriva

Spiriva Respimat

Once daily

Umeclidinium

Incruse Ellipta

Twice daily Aclidinium

Bretaris Genuair

LABA–LAMA combinations*

Once daily

Indacaterol + glycopyrronium

Ultibro Breezhaler

Once daily

Olodaterol + tiotropium

Spiolto Respimat

Once daily

Vilanterol + umeclidinium

Anoro Ellipta

Twice daily

Formoterol + aclidinium

Brimica Genuair

  • * Ensure that patient is also using regular long-term ICS. LABAs and LAMAs should not be used by people with asthma or asthma–COPD overlap unless they are also taking an ICS, in combination or separately)
  • Advise patients/carers that inhalers should be stored below 30°C and should not be left in cars.

The inhaler must be discarded 1 month after opening the package and removing device from tray. When first opened, patients should write the discard date on the label in the space provided. If stored in the refrigerator, inhaler should be taken out and allowed to return to room temperature for at least an hour before use.

The inhaler must be discarded 6 weeks after opening the package and removing device from tray. When first opened, patients should write the discard date on the label in the space provided. If stored in the refrigerator, inhaler should be taken out and allowed to return to room temperature for at least an hour before use.

# Only the 100/25 microg dose of fluticasone furoate/vilanterol is TGA-approved for treatment of COPD. The higher dose (200/25 microg) is not TGA-approved for the treatment of COPD, so it should not be used in people with asthma–COPD overlap.

High doses of ICS (alone or in combination) are not recommended in patients with COPD and should therefore be used with caution in patients with asthma-COPD overlap, because of the risk of pneumonia.

Refer to PBS status before prescribing.

Last reviewed version 2.0

Asset ID: 105

Close

Management should also include smoking cessation, treatment of comorbid conditions, physical activity, pulmonary rehabilitation, vaccinations, self-management (including a regularly updated action plan) and regular follow-up.54

Respiratory tract infections should be monitored carefully because people with asthma–COPD overlap have high morbidity rates and because ICS treatment is associated with increased risk of non-fatal pneumonia in people with COPD.66 Most of the available evidence is from patients treated with fluticasone propionate, particularly at higher doses. Increased pneumonia rates have also been observed in studies of patients with COPD using fluticasone furoate/vilanterol. The higher dose of fluticasone furoate/vilanterol (Breo Ellipta 200/25 microg) is not approved for patients with COPD, so it should also not be used in patients with asthma–COPD overlap.

Specialist referral should be considered for patients with atypical symptoms or symptoms that suggest an alternative diagnosis, persistent symptoms or flare-ups despite treatment, or complex comorbidities.

For information on diagnosis and management of COPD, refer to the COPD-X Concise Guide for Primary Care.67

Last reviewed version 2.0

Close
Effects of gastro-oesophageal reflux disease treatment on asthma

Adults with gastro-oesophageal reflux disease

In adults with asthma and a diagnosis of gastro-oesophageal reflux disease, treatment with a proton pump inhibitor (esomeprazole, lansoprazole, omeprazole, pantoprazole or rabeprazole) produces a small increase in lung function and improves quality of life.68 There is insufficient evidence from randomised controlled clinical trials to determine whether proton pump inhibitor treatment improves asthma symptoms in patients with gastro-oesophageal reflux disease.68

The combination of a proton pump inhibitor and domperidone may improve lung function and asthma symptoms in adults with asthma and gastro-oesophageal reflux disease.6970

Earlier small studies of H2-antagonists (conducted before proton pump inhibitors became the standard first-line medical treatment for gastro-oesophageal reflux disease) reported inconsistent effects of ranitidine and cimetidine on lung function and other asthma outcomes.713772 In patients with a history of asthma symptoms related to reflux symptoms, H2-antagonist treatment may reduce night-time symptoms and reliever requirement.71

A small study reported that antireflux surgery was more effective than ranitidine for improving asthma symptoms in adults with asthma and gastro-oesophageal reflux disease.73

Children with gastro-oesophageal reflux disease

Limited evidence from randomised controlled clinical trials suggests that proton pump inhibitor treatment (lansoprazole, omeprazole) does not improve asthma in children with gastro-oesophageal reflux disease.7475

Clinical trials have not investigated the effects of reflux treatment on asthma in children aged 5 years and under.

Subclinical gastro-oesophageal reflux disease

Subclinical or undiagnosed gastro-oesophageal reflux disease is sometimes thought to contribute to asthma symptoms or poorly controlled asthma, leading to the hypothesis that reflux treatment may be useful in asthma treatment. However, clinical trial findings do not support this strategy:

  • In adults with asthma but without confirmed gastro-oesophageal reflux disease, proton pump inhibitor treatment achieves a small increase in lung function that is unlikely to be clinically important.68
  • In children with poorly controlled asthma but no symptoms of gastro-oesophageal reflux disease, lansoprazole treatment did not improve asthma symptom or lung function, but was associated with increased adverse events (mainly respiratory infections).74
Close
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.76

Obese people may have a reduced response to inhaled corticosteroids, compared with non-obese people.77, 78, 79  However, inhaled corticosteroids are still effective in obese people.80 Compared to people with normal BMI, people with BMI > 40 may take longer to achieve peak FEV1 after starting preventer treatment.79

There is also some evidence of a reduced response to montelukast among obese patients, but findings are not consistent.78, 79

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.81

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.8182 However, weight loss has not been shown to achieve clinically important improvement in lung function.81

Some recent case series studies have found that adults who underwent bariatric surgery (various procedures) were able to reduce their inhaled corticosteroid dose.8384

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.85 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.85

In a small study in Australian children, a dietary weight loss intervention was associated with improvement in lung function, compared with baseline.86

Last reviewed version 2.0

Close
Effects of mental health treatments on asthma

Few randomised controlled clinical trials have investigated whether specific treatments for depression or anxiety in people with asthma can improve symptom control or overall function:87 In one placebo-controlled antidepressant trial, improvement in depression was associated with improvement in asthma control, irrespective of treatment received.88

Other studies have reported psychosocial benefits with various interventions:

  • In highly anxious patients with asthma, a brief cognitive behavioural intervention may reduce asthma-specific fear.5
  • Asthma self-management education and asthma monitoring (either written information and frequent follow-up, or more intensive coaching) has been associated with improvement in quality of life, particularly among patients with depressive symptoms.89
  • Physical activity (aerobic training) has been associated with improvement in anxiety and depression in people with asthma.90
Close
Screening for depression

There is a range of validated screening tools that can be used to identify symptoms of mental illness, including depression and anxiety. For adults, asking two simple screening questions in primary care can help identify those who need further investigation for depression:91

Over the past 2 weeks, have you felt down, depressed or hopeless?

Over the past 2 weeks, have you felt little interest or pleasure in doing things?

A list of screening and assessment tools appropriate for adolescents and young adults is included in beyondblue’s Clinical practice guidelines: Depression in adolescents and young adults (2010).92

Close
Discussing complementary medicines with patients

For more information about discussing complementary medicines with patients and monitoring their effects, refer to National Asthma Council Australia’s information paper for health professionals Asthma and complementary therapies.93

Close

References

  1. 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
  2. Alvarez GG, Fitzgerald JM. A systematic review of the psychological risk factors associated with near fatal asthma or fatal asthma. Respiration. 2007; 74: 228-36. Available from: http://www.karger.com/Article/FullText/97676
  3. Boulet LP. Influence of comorbid conditions on asthma. Eur Respir J. 2009; 33: 897-906. Available from: http://erj.ersjournals.com/content/33/4/897.long
  4. Lavoie KL, Boudreau M, Plourde A, et al. Association between generalized anxiety disorder and asthma morbidity. Psychosom Med. 2011; 73: 504-13. Available from: http://www.psychosomaticmedicine.org/content/73/6/504.long
  5. Parry GD, Cooper CL, Moore JM, et al. Cognitive behavioural intervention for adults with anxiety complications of asthma: prospective randomised trial. Respir Med. 2012; 106: 802-10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22398158
  6. Theoharides TC, Enakuaa S, Sismanopoulos N, et al. Contribution of stress to asthma worsening through mast cell activation. Ann Allergy Asthma Immunol. 2012; 109: 14-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22727152
  7. Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics. 2007; 120: 855-864. Available from: http://pediatrics.aappublications.org/content/120/4/855.full
  8. Szefler, SJ, Phillips, BR, Martinez, FD, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005; 115: 233-242. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15696076
  9. 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
  10. Basheti, IA; Obeidat, NM; Reddel, HK;. Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.. NPJ Prim Care Respir Med. 2017; 27: 9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28184045
  11. 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
  12. Aldea Perona, A., Garcia-Saiz, M., Sanz Alvarez, E.. Psychiatric disorders and montelukast in children: a disproportionality analysis of the VigiBase®. Drug Saf. 2016; 39: 69-78. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26620206
  13. Valovirta, E., Boza, M. L., Robertson, C. F., et al. Intermittent or daily montelukast versus placebo for episodic asthma in children. Ann Allergy Asthma Immunol. 2011; 106: 518-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21624752
  14. Harmanci, K, Bakirtas, A, Turktas, I, Degim, T. Oral montelukast treatment of preschool-aged children with acute asthma. Ann Allergy Asthma Immunol. 2006; 96: 731-735. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16729788
  15. 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
  16. National Asthma Council Australia,. Monoclonal antibody therapy for severe asthma. An information paper for health professionals.. NACA, Melbourne, 2018.
  17. Kooi, EM, Schokker, S, Marike Boezen, H, et al. Fluticasone or montelukast for preschool children with asthma-like symptoms: randomized controlled trial. Pulm Pharmacol Ther. 2008; 21: 798-804. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18647656
  18. 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
  19. 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
  20. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008; 122: 1127-1135. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18973936
  21. Schumock GT, Stayner LT, Valuck RJ, et al. Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study. J Allergy Clin Immunol. 2012; 130: 368-75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22698520
  22. Wallerstedt SM, Brunlöf G, Sundström A, Eriksson AL. Montelukast and psychiatric disorders in children. Pharmacoepidemiol Drug Saf. 2009; 18: 858-864. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19551697
  23. Philip G, Hustad C, Noonan G, et al. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 691-6.e6. Available from: http://www.jacionline.org/article/S0091-6749(09)01247-0/fulltext
  24. Philip G, Hustad CM, Malice MP, et al. Analysis of behavior-related adverse experiences in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 699-706.e8. Available from: http://www.jacionline.org/article/S0091-6749(09)01248-2/fulltext
  25. Szefler, S. J., Carlsson, L. G., Uryniak, T., Baker, J. W.. Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol Pract. 2013; 1: 58-64. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24229823
  26. Knorr, B, Franchi, LM, Bisgaard, H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pedriatrics. 2001; 108: E48. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11533366
  27. Diepgen TL, Early Treatment of the Atopic Child Study Group. Long-term treatment with cetirizine of infants with atopic dermatitis: a multi-country, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002; 13: 278-86. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12390444/
  28. Brodlie M, Gupta A, Rodriguez-Martinez CE, et al. Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children. Cochrane Database Syst Rev. 2015; Issue 10: CD008202. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26482324
  29. Robertson, CF, Price, D, Henry, R, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007; 175: 323-329. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17110643
  30. Nwokoro C, Pandya H, Turner S, et al. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med. 2014; 2: 796-803. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25212745
  31. Giraud, V., Allaert, F. A., Roche, N.. Inhaler technique and asthma: feasability and acceptability of training by pharmacists. Respir Med. 2011; 105: 1815-22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21802271
  32. Ciolkowski, J., Mazurek, H., Stasiowska, B.. Evaluation of step-down therapy from an inhaled steroid to montelukast in childhood asthma. Allergol Immunopathol (Madr). 2014; 42: 282-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23684855
  33. Nagao M, Ikeda M, Fukuda N, et al. Early control treatment with montelukast in preschool children with asthma: a randomized controlled trial. Allergol Int. 2018; 67: 72-78. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28526210
  34. Kew KM, Beggs S, Ahmad S. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015; Issue 5: CD011316. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25997166
  35. Kew, KM; Quinn, M; Quon, B. S; Ducharme, FM;. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev. 2016; Issue 6: CD007524: . Available from: https://www.ncbi.nlm.nih.gov/pubmed/27272563
  36. Rank, M. A., Johnson, R., Branda, M., et al. Long-term outcomes after stepping down asthma controller medications: a claims-based, time-to-event analysis. Chest. 2015; 148: 630-639. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556120/
  37. Jacobsen, L., Niggemann, B., Dreborg, S., et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy. 2007; 62: 943-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17620073
  38. Pike, K. C., Akhbari, M., Kneale, D., Harris, K. M.. Interventions for autumn exacerbations of asthma in children. Cochrane Database Syst Rev. 2018; Issue 3: Cd012393. Available from: http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD012393.pub2/full
  39. Mann, RD; Pearce, GL; Dunn, N; Shakir, S. Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice. BMJ (Clinical research ed). 2000; 320: 1184-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10784544
  40. Ducharme, F. M., Noya, F. J., Allen-Ramey, F. C., et al. Clinical effectiveness of inhaled corticosteroids versus montelukast in children with asthma: prescription patterns and patient adherence as key factors. Curr Med Res Opin. 2012; 28: 111-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22077107
  41. Garcia Garcia, ML, Wahn, U, Gilles, L, et al. Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: The MOSAIC Study. Pediatrics. 2005; 116: 360-369. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16061590
  42. Fonseca-Aten, M, Okada, P J, Bowlware, K L, et al. Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2006; 97: 457-463.
  43. Philip, G, Hustad, C, Noonan, G, et al. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 691-696. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19815114
  44. Philip, G., Hustad, C. M., Malice, M. P., et al. Analysis of behavior-related adverse experiences in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 699-706. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19815116
  45. Ali, M. M., O'Brien, C. E., Cleves, M. A., Martin, B. C.. Exploring the possible association between montelukast and neuropsychiatric events among children with asthma: a matched nested case-control study. Pharmacoepidemiol Drug Saf. 2015; 24: 435-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25683909
  46. Therapeutic Goods Administration,. Montelukast – neuropsychiatric risks. Aust Prescr. 2013; 36: 168-171. Available from: https://www.nps.org.au/australian-prescriber/articles/medicines-safety-update-2-58#article
  47. Schumock, G T, Stayner, L T, Valuck, R J, et al. Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study. J Allergy Clin Immunol. 2012; 130: 368-375. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22698520
  48. 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/
  49. 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/
  50. Seqirus. Product Information: Grazax. Therapeutic Goods Administration, Canberra, 2017. Available from: https://www.ebs.tga.gov.au
  51. Stallergenes. Product Information: Oralair (allergen pollen extract of five grasses). Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/
  52. Australasian Society of Clinical Immunology and Allergy (ASCIA). Allergen Immunotherapy. ASCIA, Sydney, 2013. Available from: http://www.allergy.org.au/patients/allergy-treatment/immunotherapy
  53. Knorr, B, Matz, J, Bernstein, JA, et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast Study Group. JAMA. 1998; 279: 1181-1186. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9555757
  54. Zeiger, RS, Szefler, SJ, Phillips, BR, et al. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol. 2006; 117: 45-52. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16387583
  55. Becker, A, Swern, A, Tozzi, C A, et al. Montelukast in asthmatic patients 6 years-14 years old with an FEV1 > 75%. Curr Med Res Opin. 2004; 20: 1651-1659. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15462699
  56. Gibson PG, Simpson JS. The overlap syndrome of asthma and COPD: what are its features and how important is it?. Thorax. 2009; 64: 728-735. Available from: http://thorax.bmj.com/content/64/8/728.full
  57. Stempel, D. A., Szefler, S. J., Pedersen, S., et al. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016; 375: 840-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27579634
  58. McDonald VM, Higgins I, Gibson PG. Managing older patients with coexistent asthma and chronic obstructive pulmonary disease. Drugs Aging. 2013; 30: 1-17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23229768
  59. Reed CE. Asthma in the elderly: diagnosis and management. J Allergy Clin Immunol. 2010; 126: 681-7; quiz 688-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20673985
  60. Rabinovitch, N., Mauger, D. T., Reisdorph, N., et al. Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma. J Allergy Clin Immunol. 2014; 133: 350-6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24084071/
  61. Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010; 362: 975-985. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1001278#t=article
  62. Papadopoulos, N. G., Philip, G., Giezek, H., et al. The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity. J Asthma. 2009; 46: 413-20. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19484680
  63. Carroll, W. D., Jones, P. W., Boit, P., et al. Childhood evaluation of salmeterol tolerance–a double-blind randomized controlled trial. Pediatr Allergy Immunol. 2010; 21: 336-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19725893
  64. Fogel, R. B., Rosario, N., Aristizabal, G., et al. Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children. Ann Allergy Asthma Immunol. 2010; 104: 511-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20568384
  65. Adler, A., Uziel, Y., Mei-Zahav, M., Horowitz, I.. Formoterol induces tolerance to the bronchodilating effect of Salbutamol following methacholine-provocation test in asthmatic children. Pulm Pharmacol Ther. 2006; 19: 281-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16169761
  66. Pharmaceutical Benefits Scheme,. Post-market review. PBS medicines used to treat asthma in children. Report to PBAC. Final Report. 2017.
  67. Akashi K, Mezawa H, Tabata Y, et al. Optimal step-down approach for pediatric asthma controlled by salmeterol/fluticasone: A randomized, controlled trial (OSCAR study). Allergol Int. 2016; 65: 306-11. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27155753
  68. Chan WW, Chiou E, Obstein KL, et al. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med. 2011; 171: 620-9. Available from: http://archinte.jamanetwork.com/article.aspx?articleid=227086
  69. Huang, L., Chen, Q., Zhao, Y., et al. Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. J Asthma. 2015; 52: 16-25. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25162303
  70. van Meel, E. R., Jaddoe, V. W. V., Bonnelykke, K., et al. The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review. Pediatr Pulmonol. 2017; 52: 1363-1370. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28869358
  71. Weiler, J M, Anderson, S D, Randolph, C, et al. Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a practice parameter. Ann Allergy Asthma Immunol. 2010; 105(6 Suppl): S1-S47.
  72. den Dekker, H. T., Sonnenschein-van der Voort, A. M. M., de Jongste, J. C., et al. Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children. J Allergy Clin Immunol. 2016; 137: 1026-1035. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26548843
  73. Lis-Swiety, A., Milewska-Wrobel, D., Janicka, I.. Dietary strategies for primary prevention of atopic diseases - what do we know?. Dev Period Med. 2016; 20: 68-74. Available from: http://medwiekurozwoj.pl/articles/2016-1-9.pdf
  74. Holbrook JT, Wise RA, Gold BD, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. 2012; 307: 373-81. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22274684
  75. Thavagnanam, S., Fleming, J., Bromley, A., et al. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy. 2008; 38: 629-33. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18352976
  76. Farah CS, Kermode JA, Downie SR, et al. Obesity is a determinant of asthma control, independent of inflammation and lung mechanics. Chest. 2011; 140: 659-66. Available from: http://journal.publications.chestnet.org/article.aspx?articleid=1088127
  77. Boulet LP, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med. 2007; 101: 2240-7. Available from: http://www.resmedjournal.com/article/S0954-6111(07)00284-3/fulltext
  78. Peters-Golden M, Swern A, Bird SS, et al. Influence of body mass index on the response to asthma controller agents. Eur Respir J. 2006; 27: 495-503. Available from: http://erj.ersjournals.com/content/27/3/495.long
  79. Camargo CA, Boulet LP, Sutherland ER, et al. Body mass index and response to asthma therapy: fluticasone propionate/salmeterol versus montelukast. J Asthma. 2010; 47: 76-82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20100025
  80. Sutherland ER, Camargo CA, Busse WW, et al. Comparative effect of body mass index on response to asthma controller therapy. Allergy Asthma Proc. 2010; 31: 20-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20167142
  81. Adeniyi FB, Young R. Weight loss interventions for chronic asthma. Cochrane Database Syst Rev. 2012; 7: CD009339. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009339.pub2/full
  82. Juel CT, Ali Z, Nilas L, Ulrik CS. Asthma and obesity: does weight loss improve asthma control? a systematic review. J Asthma Allergy. 2012; 5: 21-6. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392696/
  83. Kero, J., Gissler, M., Gronlund, M. M., et al. Mode of delivery and asthma -- is there a connection?. Pediatr Res. 2002; 52: 6-11. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12084840
  84. Almqvist, C., Cnattingius, S., Lichtenstein, P., Lundholm, C.. The impact of birth mode of delivery on childhood asthma and allergic diseases--a sibling study. Clin Exp Allergy. 2012; 42: 1369-76. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22925323
  85. Scott HA, Gibson PG, Garg ML, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy. 2013; 43: 36-49. Available from: http://onlinelibrary.wiley.com/doi/10.1111/cea.12004/full
  86. Jensen ME, Gibson PG, Collins CE, et al. Diet-induced weight loss in obese children with asthma: a randomized controlled trial. Clin Exp Allergy. 2013; 43: 775-84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23786284
  87. Van Lieshout RJ, Macqueen GM. Relations between asthma and psychological distress: an old idea revisited. Chem Immunol Allergy. 2012; 98: 1-13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16757162
  88. Brown ES, Howard C, Khan DA, Carmody TJ. Escitalopram for severe asthma and major depressive disorder: a randomized, double-blind, placebo-controlled proof-of-concept study. Psychosomatics. 2012; 53: 75-80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22221724
  89. Mancuso CA, Sayles W, Allegrante JP. Randomized trial of self-management education in asthmatic patients and effects of depressive symptoms. Ann Allergy Asthma Immunol. 2010; 105: 12-9. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964839/
  90. Tischer, C, Chen, C M, Heinrich, J. Association between domestic mould and mould components, and asthma and allergy in children: a systematic review. Eur Respir J. 2011; 38: 812-824.
  91. Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 8th edn. Royal Australian College of General Practitioners, East Melbourne, 2012. Available from: http://www.racgp.org.au/your-practice/guidelines/redbook/
  92. Beyondblue. Clinical practice guidelines: Depression in adolescents and young adults. beyondblue: the national depression initiative, Melbourne, 2010. Available from: https://www.beyondblue.org.au/health-professionals/clinical-practice-guidelines
  93. National Asthma Council Australia. Asthma and complementary therapies. National Asthma Council Australia, Melbourne, 2012. Available from: http://www.nationalasthma.org.au/publication/asthma-complementary-therapies-hp