Asthma Management Handbook

Asthma prevention in children at risk of developing asthma

Recommendations

Advise parents to ensure babies and children are not exposed to cigarette smoke.

How this recommendation was developed

Adapted from existing guidance

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

  • Prescott and Tang, 20051

If a family already has pets, it is not necessary to remove them unless the child develops evidence of pet allergy and this is confirmed by skin-prick testing.

How this recommendation was developed

Adapted from existing guidance

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

  • Prescott and Tang, 20051

In children without demonstrated specific hypersensitivities, do not routinely recommend allergen avoidance measures for the purpose of reducing the child’s risk of developing 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):

  • Arshad et al. 19922
  • Arshad et al. 20033
  • Arshad et al. 20074
  • Brunekreef et al. 20025
  • Corver et al. 20066
  • Custovic et al. 20017
  • Halmerbauer et al. 20038
  • Hide et al. 19949
  • Hide et al. 199610
  • Horak et al. 200411
  • Koopman et al. 200212
  • Maas et al. 200913
  • Marks et al. 200614
  • Mihrshahi et al. 200315
  • Peat et al. 200416
  • Scott et al. 201217
  • Woodcock et al. 200418

Advise parents of children at risk of asthma that damp, mouldy home environments may increase asthma risk in children with genetic predisposition to asthma and should be avoided if possible (e.g. by ventilation and mould removal), but that there is not clear evidence that anti-mould strategies will prevent asthma.

Note: Exposure to potentially harmful fumes from chemicals in cleaning products (e.g. chlorine bleach) should also be avoided.

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):

  • Mendell et al. 201119
  • Quansah et al. 201220
  • Tischer et al. 201121
  • Tischer et al. 201122

Advise parents that children’s risk of developing asthma may be increased by various types of indoor and outdoor pollution (e.g. unflued gas heaters, traffic pollution).

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):

  • Bernstein, 201223
  • Gasana et al. 201224
  • Lanphear et al. 200125

Advise parents to give children paracetamol at recommended doses when necessary to reduce fever (according to current guidelines for managing fever) and for pain relief when needed (according to current guidelines for managing pain in children), but to avoid unnecessary or frequent paracetamol use.

How this recommendation was developed

Based on selected evidence

Based on a limited structured literature review or published systematic review, which identified the following relevant evidence:

  • Amberbir et al. 201126
  • Bakkeheim et al. 201127
  • Etminan et al. 200928
  • Foliaki et al. 200829
  • Kreiner-Møller et al. 201230
  • Kurukulaaratchy et al. 201231
  • Lowe et al. 201032
  • Wickens et al. 201133

In children with atopic dermatitis or allergic rhinitis, manage according to current guidelines (using antihistamines, if indicated) but do not prescribe or recommend long-term antihistamine use specifically for the purpose of reducing the child’s risk of developing 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):

  • Early Treatment of the Atopic Child Study Group, 199834

More information

Factors reported to be associated with increased risk of developing asthma

Many factors have been associated with asthma risk in observational studies, but none have been shown to cause asthma directly. Avoidance or correction of these risk factors has not been shown to prevent asthma developing.

Allergies

A family history of allergy is associated with a high risk of allergic disease, including asthma.1

Several population-based studies have observed a positive association between sensitisation to aeroallergens (e.g. house dust mite and cat allergens) and the development of asthma (measured by various outcomes including wheeze, diagnosed asthma, or bronchial hyperresponsiveness), and other allergic diseases including atopic dermatitis (eczema) and rhinitis.35

Although sensitisation to allergens is associated with development of allergic asthma, it is unclear whether exposure to these allergens actually causes asthma.35 The combination of sensitisation to aeroallergens and viral infections early in life increases asthma risk.36

Epidemiological studies have consistently reported an association between exposure to indoor dampness and mould, and increased risk of developing asthma or wheeze.19, 202137

Rhinitis is a major risk factor for asthma and often precedes it.383940 Childhood allergic rhinitis increases the probability of asthma developing after childhood and the probability of having persisting asthma from childhood into middle age.39 These associations probably reflect the common allergic causes of both conditions, rather than a causal link. Non-allergic rhinitis is also a predictor of adult-onset asthma.40

Note: Although allergic asthma is common, non-allergic asthma also occurs

Genetics

Several genes associated with increased risk of asthma have been identified.41 However, these genes explain very little of the inherited basis of asthma.

Asthma risk may be increased by the interaction between asthma susceptibility genes and environmental factors.42

Other influences on immune system

Exposure to tobacco smoke toxins in utero or in infancy has been associated with increased risk of developing asthma.43

Observational studies have identified various factors associated with increased risk of developing asthma. However, avoidance of these ‘risk’ factors has not been shown to prevent asthma and is not recommended specifically as a strategy for prevention of asthma (regardless of any other potential health benefits). These factors include:

  • delivery by Caesarean section (possibly related to the fact that children born by Caesarean section have modified intestinal bacterial colonisation)44
  • the use of broad-spectrum antibiotics (macrolides or cephalosporins) in early childhood45 or pregnancy46
  • the use of paracetamol during pregnancy and infancy472827303332
  • some childhood infections (pertussis and measles)48
  • respiratory infections during the first two years of life.49505152,5354555657, 36 Early life viral infection in infants sensitised to aeroallergens is a strong risk factor for acute severe asthma-like symptoms and for developing asthma that persists into adulthood.36

Observational studies have identified various factors associated with reduced risk of developing asthma. However, deliberate exposure to these ‘protective’ factors has either not been investigated in good quality studies, or has not been shown to prevent asthma and is not routinely recommended for asthma prevention.  Identified factors include:

  • exposure to farm environments and contact with farm animals58
  • diets rich in oily fish59
  • some childhood viral and bacterial infections48
  • regular long-term low-dose aspirin use by adults.60
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Effects of prenatal and postnatal maternal smoking on asthma risk

Meta-analysis of data from cohort studies suggests that:

  • smoking during pregnancy increases the child’s risk of asthma before age 2 years by an estimated 85%43
  • in children aged 0–2 years, the risk of wheezing is increased by an estimated 70% if their mothers smoke.43

Although maternal smoking during pregnancy and exposure to cigarette smoke in early childhood significantly increase the risk of wheezing illness in early childhood, they probably do not increase the risk of allergic asthma later in life.6162

Data from a case-control study suggests that smoking during pregnancy not only increases the risk of asthma in children, but also the woman’s grandchildren.63

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Allergen avoidance in children

Exposure to pets

Pooled analysis of a large set of data from 11 European birth cohorts suggests that living with a furry or feathered pet during infancy neither increases nor decreases the risk of asthma or allergic rhinitis at ages 6–10 years, compared with no exposure to pets.64

House dust mite avoidance in newborns

House dust mite avoidance measures alone are unlikely to prevent a child developing wheezing or asthma, based on the findings of randomised controlled trials in prenatally recruited infants at risk of allergies and asthma due to family history or demonstrated sensitisation,6512, 161415, 118718 including an Australian study that compared house dust mite avoidance (acaricide and impermeable mattress covers) with simple advice on cleaning, vacuuming, dusting and maintaining adequate ventilation and followed children from 18 months to 11 years.16141565

In one randomised controlled trial of prenatally recruited infants at high risk of allergies and asthma (both parents atopic), prenatal and postnatal house dust mite avoidance (mite-impermeable mattress, pillow and quilt covers, HEPA filter vacuum cleaner, replacement of carpet with vinyl flooring, custom cot and basinet mattresses, washable soft toy, hot washing of bed linen, acaricide) was associated with reduced rates of wheezing during the first year of life compared with usual care,7 but respiratory symptoms at age 3 years did not differ between intervention and control groups.18

Multi-allergen avoidance in newborns

While interventions involving a single strategy have not been successful in reducing asthma risk, multifaceted interventions that involve dietary allergen reduction and environmental allergen avoidance from birth or prenatally may reduce asthma risk.13 A systematic review and meta-analysis of randomised controlled trials assessing allergen avoidance commenced prenatally or at birth found that reduction of exposure to multiple allergens reduces the likelihood of a current diagnosis of asthma in children (at ages younger than 5 years, and 5 years and older), compared with usual care.13 The risk of doctor-diagnosed asthma at age 5 and over was approximately halved.

In a randomised controlled clinical trial that compared the combination of hypoallergenic infant diet (extensively hydrolysed formula or breastfeeding with mothers on low-allergen diet) and house dust mite avoidance strategies (acaricide and impermeable mattress covers) with standard advice,41731092  the intervention group showed lower rates of asthma at ages 1 year,102 8 years,3 and 18 years,17 but no difference between intervention and control group in asthma rates at 2 years109 and 4 years.10 The reduction in asthma prevalence at 18 years and overall prevalence was mainly due to a reduced rate of asthma that developed in childhood and persisted to 18 years.17

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Effects of pollutants on asthma risk

Exposure to a range of indoor and outdoor airborne pollutants has been associated with increased asthma risk in cross-sectional surveys.

Exposure to the following during early childhood has been associated with increased risk of wheezing or asthma:

  • the use of gas stoves or ovens in homes25
  • living in damp or mouldy environments19, 202137
  • high exposure to traffic pollution.2324

Various indoor and outdoor pollutants have also been associated with increased risk of adult-onset asthma. These include airborne substances used in the home (e.g. cleaning sprays66) and many airborne substances encountered in workplaces.

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Links between paracetamol and asthma risk

Prenatal exposure

Meta-analyses of data from prospective cohort studies and cross-sectional surveys have identified an association between prenatal exposure to paracetamol and increased risk of asthma and wheeze in children.4728

Health professionals can advise pregnant women that there is some evidence from around the world that paracetamol use in pregnancy might increase the baby’s risk of wheezing or asthma, but that paracetamol is still considered the best option for pain relief in pregnant women.67

Paracetamol use in children

Meta-analysis of cross-sectional population studies observed paracetamol use in previous year, and paracetamol use in first year of life, each associated with increased risk of asthma diagnosis in children aged 4–16 years.28

Some prospective cohort studies have reported an association between paracetamol use in infants,272630 children3329 or adolescents31 and increased risk of wheezing or asthma. However, an Australian study observed no association between paracetamol use and asthma risk after adjusting for frequency of respiratory infections.32

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Children’s diets and asthma risk

In observational studies, various dietary factors have been associated with increased asthma risk. For example:

  • ‘Western’-style fast food intake has been shown to increase asthma risk in children68697071
  • consumption of a ‘westernised’ diet has been associated with increased asthma risk, compared with an ‘Asian’ diet70
  • a diet high in fast foods has been associated with increased childhood asthma prevalence71
  • a ‘Mediterranean’ diet (high in fish, fruits and vegetables) may provide some protection against wheeze and asthma in childhood.72

Further research is needed to determine if these associations are due to causal links between food choices and asthma risk, and randomised controlled trials are needed to show whether changes in eating patterns can improve asthma or reduce the risk of developing asthma.

Supplementation with probiotics (Lactobacillus rhamnosus) in children aged 6 months to 2 years may reduce sensitisation to aeroallergens, but has not been shown to reduce risk of developing asthma, based on the findings of one randomised clinical trial.73

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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.74, 75 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.76, 77, 78 There is less evidence supporting specific allergen immunotherapy in children than in adults.77 Specific allergen immunotherapy in children with seasonal allergic rhinoconjunctivitis might prevent development of asthma.79, 80

Single-allergen specific allergen immunotherapy is effective in patients sensitised to one allergen and those sensitised to multiple allergens.81, 82, 83 In selected cases more than one allergen may be administered as separate extracts. There is weak evidence for the efficacy of allergen mixes.84

A systematic review of studies directly comparing subcutaneous immunotherapy and sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma found:85

  • 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.86, 87, 88

Sublingual immunotherapy

Sublingual immunotherapy (self-administered at home) is effective for the treatment of allergic rhinitis in adults and children.89 90 The greatest benefits have been demonstrated in those with allergies to temperate grass pollens or house dust mite.90 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.89 Local adverse effects are common in children receiving sublingual immunotherapy.86 Systemic adverse reactions, such as anaphylaxis, are very rare.86 The majority of adverse events occur soon after beginning treatment.90

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.91 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.91

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.91
  • 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.92
  • Grazax (Timothy grass [Phleum pratense] pollen extract) – indicated for adults, adolescents and children older than 5 years with allergic rhinitis induced by Timothy grass93
  • Oralair tablets (mix of grass pollens) – indicated for adults and children over 5 years with grass pollen allergic rhinitis.94

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.95 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.87 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.87 There is also moderate evidence that subcutaneous immunotherapy reduces rhinitis/rhinoconjunctivitis medication usage.87

Subcutaneous immunotherapy is associated with local adverse effects (e.g. injection-site swelling) and, less frequently, serious systemic adverse effects.86, 90 The most common systemic reactions are respiratory symtoms. There have been few reports of anaphylaxis.87

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

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Antihistamines in children with allergies

Long-term antihistamine treatment has been investigated as a strategy for preventing the development of asthma in children with allergies.

In a multi-country, double-blind, randomised, placebo-controlled trial in children aged 1–2 years with atopic dermatitis,34 18 months’ treatment with cetirizine (0.25mg/kg twice daily) did not reduce the risk of developing asthma, compared with placebo. However, in the subgroup of children sensitised to grass pollen or house dust mite, cetirizine treatment was associated with a reduction in the rate of new asthma diagnoses, compared with placebo.34

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References

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