Intermittent or persistent asthma? Which inhaled corticosteroid? The role of long acting beta-2 agonists (LABA). Role of nebulisers in childhood asthma. What is the place of mast cell stabilisers, sodium cromoglycate and nedocromil? Paracetamol and the link with asthma.
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Is it asthma? Is a preventer indicated; which one and what dose?
What triggers attacks? What delivery device ?
These are just some of the questions that can arise when dealing with childhood asthma. In this section we present some
short topics of interest.
Intermittent or persistent asthma and the role of preventers
It is important to obtain the historical pattern of asthma symptoms to determine if asthma is persistent or intermittent
and the need for regular preventer treatment. If the pattern of symptoms is uncertain, consider the use of a symptom diary
or organise frequent reviews until the pattern becomes clear.
Infrequent intermittent asthma
About 75% of children with asthma have infrequent intermittent asthma2 in which children
have isolated episodes of asthma lasting from 1–2 days up to 1–2 weeks. Characteristics of infrequent intermittent asthma
- triggered by URTI or environmental allergen
- episodes more than 6–8 weeks apart
- asymptomatic in the interval periods
Although the severity of episodes varies, most are relatively mild but they still account for a significant number of
Regular preventive therapy is not usually recommended for infrequent intermittent asthma. Management involves recognition
and treatment of symptoms, reducing the risk of infections and minimising exposure to triggers. Complete avoidance of
exposure to cigarette smoke is also important.
ICS may be overprescribed in this group in the mis-conception that they reduce the number of exacerbations due to viral
infections and have beneficial effects on lung function and asthma disease progression. There is no evidence to support
maintenance ICS for the prevention and management of mild episodic viral induced wheeze.12
Frequent intermittent asthma
About 20% of children with asthma have frequent intermittent asthma (more than two exacerbations per month and minimal
symptoms between episodes) and may benefit from regular preventer therapy, usually low dose ICS. The preventer may only
be required during the winter months.
About 5 – 10% of children with asthma have persistent asthma where symptoms occur on most days and often include; sleep
disturbance due to cough or wheeze, early morning chest tightness, exercise intolerance and spontaneous wheeze.
Acute asthma episodes, as in intermittent asthma, may also be superimposed on this persistent pattern. Severity ranges
from mild (daytime symptoms several times per week) to severe (continual daytime symptoms).
Regular preventive treatment is indicated for persistent asthma (usually starting with a low dose ICS) and titrated
to effect, with add on therapy as required.
Which inhaled corticosteroid?
The inhaled corticosteroid preparations available in New Zealand are listed in Table 2 (see Guide
to Asthma Management in Children). Clinically they are all equally effective at equivalent doses.
Note: 200 mcg of fluticasone is equivalent to 400 mcg of budesonide or beclomethasone.
Choice might be governed by the type of inhaler device available or intolerance to the propellant. For example:
- Switching from beclomethasone (Beclazone) to budesonide (Pulmicort) if the child is able to efficiently use a breath
- Switching to fluticasone (Flixotide) if a CFC-free preparation is preferred
- Child personal preference (e.g. what their friend has)
Safety of inhaled corticosteroids
In children, doses of ICS greater than 200 mcg/day fluticasone or 400 mcg/day beclomethasone may be associated with
systemic side-effects including growth failure and adrenal suppression. Children receiving such doses should preferably
be seen by a paediatrician and their asthma management plan should include advice about steroid replacement during severe
Common Asthma Triggers
Cigarette smoke and its constituent chemicals that are absorbed into the environment (e.g., into furniture, clothes
and cars) are irritants and can cause asthma and/or worsen symptoms.
Currently, one in ten children in New Zealand is exposed to second-hand smoke in their home.13 It
is uncertain exactly how many infants are exposed to cigarette smoke in-utero, however exposure to tobacco smoke during
key developmental stages, in-utero and a few months post-birth, greatly increases the risk of developing asthma and allergy. 14
Among teenagers who smoked, there is evidence to show that their risk of developing asthma increased four-fold if they
smoked regularly. Furthermore, the risk of developing asthma doubled if their mothers had also smoked while pregnant with
Repeated exposure to the irritants in cigarette smoke causes hyperplasia of mucous glands, leading to increased production
of mucous that accumulates in airways. Chronic inflammation of smaller airways may also occur in developing lungs, narrowing
the airways and leading to decreased lung capacity. The effects contribute to asthma symptoms and other respiratory illnesses.16
All carers of asthmatic children should be asked whether they smoke and provided with support to quit. They should also
be provided with effective ways to protect their children from the harmful effects of cigarette smoke exposure, for example,
suggest smoking outside or changing clothes before picking up young children.
Allergens can include house dust mites, pets, pollen, moulds and in rare cases, foods. If the allergen is not clear
from the history consider skin sensitivity testing.
Colds and Flu
Many children have intermittent asthma in which symptoms are only triggered by a viral infection. These children do
not generally benefit from regular preventer treatment, and the focus is on management of exacerbations and minimising
exposure to triggers, including active or passive exposure to tobacco smoke.17
Physical factors such as exercise, cold air and mould associated with damp housing can provoke asthma symptoms. Portable,
unflued gas heaters are the only source of heating in many New Zealand homes. These heaters release a significant amount
of water into the home environment. Asthma symptoms induced by environmental or seasonal changes often require increased
dose of preventer or reliever medicine as appropriate.
What is the place of mast cell stabilisers, sodium cromoglycate and nedocromil?
Sodium cromoglycate inhibits the immediate and late response to allergen challenge and is potentially
useful if used before allergen exposure in susceptible children.
It may be useful as initial preventer treatment for children with intermittent asthma or mild persistent asthma, especially
if there are reasons that an ICS cannot be used.
- Onset is slow but an effect is usually seen after one to two weeks. A four week trial is recommended before considering
- There is no additional benefit from adding sodium cromoglycate to an established regimen of ICS or oral corticosteroid
- It can be used in addition to or instead of a SABA to prevent exercise induced asthma
- No clear benefits have been shown in children aged under five years
- Side effects are minimal
- Powder for inhalation (Intal Spincaps) and aerosol (Vicrom) are partly subsidised
Nedocromil is chemically different to corticosteroids and cromoglycate. It inhibits asthmatic reactions
to allergens and exercise, and has a similar protective effect as cromoglycate against these stimuli, but is longer acting.
Nedocromil appears to have a place in the treatment of asthmatic cough due to a direct effect on sensory nerves. Any
reduction in cough usually occurs within the first two to three days.
Long acting beta-2 agonists (LABA) in treatment of asthma
There are currently two long acting beta agonists (LABAs) available in New Zealand; eformoterol (Oxis, Foradil) and
Role of LABAs
The addition of a LABA may improve lung function and reduce exacerbations in children who are still symptomatic despite
regular preventer treatment with an ICS.
For children on a standard dose of ICS (100 mcg/day fluticasone or 200 mcg/day beclomethesone) a LABA can be added as
an alternative to increasing the ICS dose. Improved symptom control may be seen also when LABA are added to higher doses
of ICS (200 mcg/day fluticasone or 400 mcg/day beclomethesone).
Research from the UK, and anecdotal experience from New Zealand, indicate that children are often prescribed higher
doses of ICS instead of the addition of a LABA. The addition of a LABA should be considered before increasing the dose
of ICS above 200 mcg/day fluticasone.
In children who are already on high dose ICS (200 mcg/day fluticasone or greater) a dose reduction may be considered
after the LABA is added.
How to use LABAs
LABAs are not preventers, but are sometimes referred to as symptom controllers. They need to be used concurrently
with an ICS.
LABAs are not licensed for use in children aged under four years (salmeterol) and under six years (eformoterol) but
may be an option as add on therapy on the advice of a paediatrician.
Good patient education is required when prescribing a LABA with the main emphasis on advising continued use of the ICS.
Many people who are switched to a LABA perceive that the ICS preventer is no longer required and either don’t pick up
repeats at their pharmacy or become less compliant. Children and their caregivers should be advised about the importance
of continuing the use of their ICS, even if the dose is reduced.
There is some concern that regular LABA use may reduce the bronchodilatory response to SABA. When a LABA is added careful
review of symptom control is required to assess whether there is any change in response to SABA. Children using LABA may
need more doses of SABA to relieve bronchoconstriction than those not using LABA and should be told about this. They should
be reminded that their new inhaler is not a reliever and to have their reliever available to use if they have symptoms.
It is recommended a short acting beta agonist (SABA) is prescribed with any LABA preparation.
Combination LABA/ICS preparations
Available preparations are salmeterol with fluticasone (Seretide) and eformoterol with budesonide (Symbicort and Vannair).
These preparations may be useful if it is considered that the patient would benefit from a combined inhaler.
Eformoterol may be used as a reliever when used in the combination ICS product but salmeterol cannot as its onset of
action is too slow (15 – 20 minutes).
Role of nebulisers in childhood asthma
Nebulisers have a limited role in childhood asthma. MDI with a spacer is as effective as a nebuliser, quicker to use,
more portable and usually more acceptable to the child and caregiver.
Indications for nebuliser use in children include;
- When the asthma is so severe that the child cannot move the spacer valve
- When the child is sensitive to the aerosol propellant
- When the child does not tolerate/refuses delivery by a spacer
The nebuliser should only be used if it delivers adequate flow. If it takes longer than five minutes to deliver 2.5
mL of solution, the airflow is inadequate for correct nebulisation. Nebulisers should be serviced at least annually.
|Optimal use of spacers
- Use a spacer with a mask for children under two years and a spacer without mask as soon as the child can breathe
consistently using the spacer mouthpiece
- The size of the spacer is relatively unimportant but small volume spacers are more convenient
- Shake the inhaler before each puff
- Deliver one puff in to the spacer at a time.
- Allow the child to breath normally through the spacer for six breaths after each puff
- Replace spacers every six months if they are used regularly
- Wash the spacer once per week using dishwashing liquid. Allow to air dry.
- A new spacer or one that has not been used for several months requires priming before use. A spacer can be primed
by washing as above or by firing ten puffs of reliever into the spacer.
Paracetamol and the link with asthma
No reason to stop using paracetamol in children for pain and fever.
A recent New Zealand study published in the Lancet found that the use of paracetamol for fever in the first year of
life was associated with increased risk of asthma, rhinoconjunctivitis or eczema at age 6 – 7 years.
The prevalence of asthma has been increasing for over 50 years but the reasons for this are not understood. During this
period the use of paracetamol has also increased. Earlier studies have shown a link between paracetamol use and asthma.
The latest study reports some findings from Phase Three of ISAAC which is an ongoing, multicentre, international study,
looking at asthma and allergies in children.
Parents of children aged 6 – 7 years were asked about their child’s use of paracetamol in the previous 12 months and
about the use of paracetamol use for fever in the child’s first year of life. Parents were asked about symptoms of wheeze
(as an indication of asthma), symptoms of itchy eyes and nose, and symptoms of itchy skin rash. Other variables such as
country of residence, age, gender, parental smoking and diet were considered.
Key Study findings
- Paracetamol use in the first year of life was associated with an increased risk of asthma symptoms (“wheezing or whistling
in the chest”) when aged 6 – 7 years (OR 1.46; 95%CI 1.36 – 1.56)
- There was an association between asthma symptoms in the previous 12 months and reported use of paracetamol in the
previous 12 months. The paracetamol use was classified as medium (at least once per year) and high (at least once per
- Medium and high current users of paracetamol were more likely to have “severe” asthma than never users.
In conclusion the authors suggest that use of paracetamol may be a risk factor for the development of asthma and other
allergic conditions. However, an observational study like this can identify signals for further investigation but not
establish causality. Some possible confounders and sources of bias identified by the authors and other commentators are;
- Recall bias; accuracy of reporting of paracetamol use and symptoms by parents
- Problems with translations and interpretations of questionnaires in different countries
- Children with the reported symptoms may have been more likely to be given paracetamol
- The symptom of wheeze has many other causes other than asthma in this age group
A causal link between the use of paracetamol and the development of asthma has not been shown but further research in
to the long term effects of paracetamol is justified. Paracetamol is still indicated for the treatment of pain and fever
but as with any medicine, it should only be used when indicated. Antipyretic drugs should not be given routinely to children
if they are otherwise well but either paracetamol or ibuprofen may be used if the child is distressed or unwell. Ibuprofen
may cause more adverse effects than paracetamol and can aggravate or provoke asthma symptoms in some children.
For more information
Beasley R. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis,
and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme. Lancet 2008; 372:1039-1048
Paracetamol associated with asthma symptoms http://www.medsafe.govt.nz/hot/alerts/ParacetamolAsthma.asp