What you need to know about asthma
Respiratory physicians Dr Hasan Arshad and Dr Suresh Babu answer questions from GP Dr David Morris on ‘safer’ steroids, long-acting ß-agonists and making asthma action plans work
Respiratory physicians Dr Hasan Arshad and Dr Suresh Babu answer questions from GP Dr David Morris on ‘safer' steroids, long-acting ß-agonists and making asthma action plans work
1 Which tests do you find most useful in diagnosing asthma? One concern with spirometry, recommended by the 2008 BTS/SIGN guidelines as being the gold-standard diagnostic test, is that it may be normal if the patient is asymptomatic at the time of the test and this wouldn't exclude the possibility of asthma.
The 2008 BTS/SIGN guidelines suggest spirometry is useful if it shows an obstructive picture and reversibility – traditionally, an improvement of more than 15% in FEV1 after inhalation of a short-acting ß2-agonist. This is highly suggestive of asthma.
But, as you quite rightly note, normal spirometry doesn't exclude the diagnosis of asthma. Those with mild asthma can have normal lung function most of the time.
Another characteristic of asthma is variability in lung function. In those with normal spirometry, we can take advantage of this characteristic by demonstrating changes in peak expiratory flow (PEF) from morning to evening and from day to day, so regular monitoring of PEF, at least twice a day for a period of two to four weeks, can help in the diagnosis.
Most patients with untreated asthma will show a variability of at least 20% in peak flows. This variability is calculated as the difference in two values – morning to evening or one day to the next – divided by the mean of two values, multiplied by 100.
If the diagnosis is still in doubt, a bronchial provocation test with non-specific stimuli such as histamine, methacholine or exercise can serve as a useful tool to demonstrate hyper-reactivity – or twitchiness – of the airways.
For those with a possible diagnosis of occupational asthma, specific bronchial provocation testing to the agent in question is considered the gold standard.
2 I recently saw a two-year-old with recurrent episodes of a wheezy cough. The parents wanted to know if this was asthma. How would you respond to this and what would be your advice on management?
It's not possible to be certain whether a two-year-old with cough and wheeze has asthma without doing elaborate tests of airway function, which requires considerable expertise and experience.
But a good history may give us enough clues. We know that most cases – about two-thirds – of infantile wheezing are due to viral infection, perhaps on a background of small airway diameter. These infants are said to have (early onset) transient wheeze, which doesn't usually develop into asthma.
Those who go on to develop asthma often have:
• a history of maternal asthma
• atopy on skin prick test
• frequent chest infections with severe wheezing episodes.
In practice – depending on the severity of episode – they need to be treated with a bronchodilator and inhaled steroid, whatever the eventual outcome. Parents can be reassured that most children will outgrow such wheeze, especially if they don't have any of the adverse prognostic signs listed above.
3 Do newer inhaled steroids mometasone and ciclesonide offer any advantage over the more traditional steroids?
Mometasone is a moderately potent steroid that is commonly used as a topical nasal and skin preparation but less commonly for asthma. It is bound by serum proteins to a higher degree than older steroids and so theoretically has an advantage in reducing systemic bioavailability.
Ciclesonide is a new generation of inhaled steroid, which is activated in the lungs and so has minimal oral or laryngeal adverse effects. It is also metabolised in the airways – after exerting its action – and so has less systemic bioavailability, making it safer than older steroids.
In asthma, systemic adverse effects are not commonly seen until the dose of inhaled steroid is increased to more than 2mg/day beclomethasone – equivalent to 1mg flixotide or budesonide – which is the level of steroid dose needed in some patients with moderate to severe asthma. Ciclesonide might be safer choice in these patients and the dose can be increased without fear of significant adverse effects.
4 I'm very tempted to use the combination inhaler of budesonide and formoterol as both a regular maintenance inhaler and as a reliever therapy when the appropriate stage of the BTS/SIGN guidelines is reached. What does the evidence say in support of this?
The 2008 BTS/SIGN guidelines suggest that the use of budesonide and formoterol in a single inhaler as reliever medication instead of a short-acting ß-agonist (in addition to its regular use as a controller treatment) is an effective treatment option in patients who are poorly controlled at step 3 of the guidelines.
Formoterol has two characteristics that make it possible to be used as a single inhaler therapy – its fast onset of effect and its dose response, meaning higher doses cause greater bronchodilation.
But careful patient education is needed when prescribing it for the first time. The licensed regimen is two inhalations per day but for some patients a maintenance dose of two inhalations twice a day may be appropriate.
Patients should take one additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, one additional inhalation should be taken. Not more than six inhalations should be taken on any single occasion and patients using more than eight inhalations daily should seek medical advice.
There is good evidence for the superior efficacy and safety of budesonide-formoterol maintenance and reliever therapy compared with two- to fourfold higher doses of budesonide plus a short-acting ß-agonist (SABA), or similar or higher doses of maintenance budesonide and formoterol, or salmeterol and fluticasone plus SABA as needed.
The budesonide-formoterol combination doesn't appear to be associated with any increased risk of adverse events compared with conventional treatment. Also, a recent Cochrane review concluded that single inhaler therapy can reduce the risk of asthma exacerbations needing oral steroids in comparison with fixed-dose maintenance inhaled steroid.
5 Can you reassure GPs on the safety of long-acting ß-agonists (LABAs) and indicate any situations in which they should be avoided?
This concern arose because LABAs are effective in treating asthma symptoms without having significant anti-inflammatory effect. So it's possible those on a LABA alone may have untreated airway inflammation but also be undertreated without an inhaled steroid.
Some clinical trials and post-marketing surveillance studies have suggested the use of a LABA in asthma, especially without an inhaled steroid, may increase mortality and/or adverse effects.
But the bulk of evidence is in favour of the use of a LABA if it's used with an inhaled steroid, which significantly reduces adverse effects, possibly by achieving optimal control of asthma at a reduced dose of inhaled steroid.
Treatment of asthma with LABA as monotherapy is not recommended as it may increase the risk of mortality.
So combined or concomitant use of LABA with an inhaled steroid should be considered best practice.
6 Are there patients in whom you would try the leukotriene receptor antagonists, montelukast and zafirlukast, sooner rather than later?
Leukotriene receptor antagonists (LTRAs) are non-steroidal treatments that are effective in asthma, in adults and children.
Adding montelukast to an inhaled steroid improves control of mild to moderate asthma compared with inhaled steroid monotherapy but is less effective than the combination of LABA with an inhaled steroid. So it's generally used as a third-line therapy, after inhaled steroid and LABA.
Some patients respond better to an LTRA than others, which may partly be genetically determined, but unfortunately, there is no test or patient profile that allows us to identify who would most benefit.
But it's reasonable to try an LTRA earlier in some patients including those:
• who prefer oral medications and have difficulty using inhalers
• with both asthma and rhinitis as LTRAs are also effective in allergic rhinitis
• with aspirin-induced asthma
• with exercise-induced asthma as montelukast provides effective protection in exercise-induced bronchospasm, both as a single dose and as regular treatments.
7 Is there any merit in increasing the dose of the steroid inhaler in a patient with deteriorating asthma or should we move straight to oral steroids?
Previous guidelines recommend doubling the dose of the inhaled steroid at the time of exacerbation as part of the asthma action plan. These recommendations are of unproven value and the latest BTS guidelines recognise this.
Three studies in adults and one in children looked at the common practice of doubling the daily dose of inhaled steroid for mild to moderately severe exacerbations and found no evidence of any benefit. The slow onset of action of inhaled steroid compared with the rapid deterioration in asthma control during an exacerbation might be a reason for this.
But it could be that simply doubling the dose of inhaled steroid is not enough.
In young children, administration of large doses of inhaled steroid through a spacer device seems to be as effective as an oral steroid for the treatment of an acute severe wheezing episode.
One study showed that a fourfold increase in maintenance treatment with budesonide reduced exacerbations needing prednisolone. It has also been shown with fluticasone and ciclesonide that large inhaled doses were as effective as oral steroids when used to treat induced deterioration in asthma control, following serial reduction in inhaled steroid dose.
So, doubling the dose of inhaled steroid is not sufficient to prevent or treat an exacerbation, although larger doses might be – but this awaits confirmation.
8 Given their potential for toxicity, is there still a role for theophyllines in the management of asthma?
Theophyllines are effective bronchodilators in asthma and also have useful anti-inflammatory properties, but their well-known potential for toxicity has reduced their use in mild to moderate asthmatic patients.
But if asthma is not adequately controlled with combined inhaled steroid and LABA – and an LTRA trial has been given – then the use of theophyllines is justified.
If monitored properly, with blood tests to ensure serum levels are within therapeutic range, there is no reason why they can't be used safely and effectively. Theophyllines work by inhibiting phosphodiesterases, although recently specific PDE4-inhibitors have been developed for asthma and COPD treatment. These have the advantage of being similarly effective but are a safer alternative. Once PDE4-inhibitors and other similar drugs become freely available and the confidence in their use increases, the role of theophyllines in the management of asthma may be further reduced.
9 Patient self-management plans have been shown to improve asthma control and reduce admissions. What are the essential elements of such a plan?
The key aspects of asthma self-management plans include:
• patient education, provided in a structured way
• encouraging patients' belief about their ability to help themselves
• regular PEF monitoring
• awareness of symptoms of worsening control
• a written self-management action plan.
The doctor prepares the plan detailing the adjustments to the patient's medications based on their asthma symptoms and/or peak flow meter readings. Generic action plans are available from various national sources such as Asthma UK, but these may need to be individualised according to the needs of the patients. Plans for both adults and children can be obtained from www.asthma.org.uk.
Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing and poor compliance to medication, and also in people with frequent exacerbations.
10 Not infrequently I see middle-aged to elderly adults who have developed chronic respiratory symptoms with an obstructive picture on spirometry. It can be difficult to decide between asthma and COPD and possibly they have a combination of both. How would you advise managing these patients?
Treat the treatable. COPD can be viewed as a spectrum with emphysema at one end and asthma at the other. Chronic bronchitis falls somewhere in the middle.
Most COPD patients have a reversible (asthmatic) component and some chronic asthmatics do show irreversibility, just like COPD patients.
The first step is to establish the extent of reversibility through the use of peak flow monitoring, spirometry and reversibility to bronchodilator and if needed, assess improvement following a course of oral or inhaled steroids. This may clarify the diagnosis toward one or the other end.
But the diagnostic label is more important for prognosis than it is for treatment. What's more important is to achieve maximal bronchodilatation and control of airway inflammation with inhaled steroids by introducing combined inhaled steroid and LABA at an earlier stage and consider using long-acting anticholinergic, theophyllines or PDE4-inhibitors, if first- and second-line treatment does not provide adequate control.
Prevention of lung function deterioration by avoidance of smoking or occupational exposure (if relevant) and other irritants and effectively treating chest infections to reduce exacerbation is also important.
Dr Hasan Arshad is a reader in asthma and allergy and honorary consultant physician at the School of Medicine, University of Southampton
Dr Suresh Babu is trainee respiratory registrar in the Wessex respiratory rotation
Competing interests None declaredAsthma What I will do now What I will do now
Dr Morris considers the responses to his questions
As pointed out, lack of reversibility and normal spirometry don't exclude asthma and it's better to regard reversibility as a means of ‘ruling-in' asthma. In patients with normal spirometry who clinically would appear to have asthma, peak-flow monitoring twice daily for a month may reveal the underlying variability that characterises asthma.
I'm reassured that use of inhaled steroid and bronchodilators in a two-year-old with cough and wheeze is a reasonable strategy, even if at this stage it's not possible to identify which children will progress to asthma.
In deteriorating asthma I think the steroid options that are supported by the evidence are to either substantially increase the dose of inhaled steroid – by at least fourfold – or perhaps more reliably to introduce oral prednisolone. I think the latter will remain my preferred option.
I am further convinced by the comments that the evidence base for using the combination inhaler of budesonide and formoterol as both a regular maintenance inhaler and a reliever therapy is robust, and I plan to use this strategy more frequently.
I'll also bear in mind the benefits of LTRAs in patients with concurrent asthma and rhinitis and consider using this option in patients with exercise-induced asthma.
Dr David Morris is a GP in Shrewsbury, Shropshire