Guidance
Rationale and impact
- Objective tests for diagnosing asthma in adults, young people and children aged 5 to 16 with a history suggestive of asthma
- Monitoring asthma control
- Principles of pharmacological treatment
- Digital inhalers
- Medicines for the initial management of newly diagnosed asthma in people aged 12 and over
- Medicine combination and sequencing in people aged 12 and over
- Transferring people aged 12 and over from other treatment pathways
- Medicines for initial management in children aged 5 to 11
- Medicine combination and sequencing in children aged 5 to 11
- Pharmacological management in children under 5
- Self-management
- Risk-stratified care
Rationale and impact
These sections briefly explain why the committee made the recommendations and how they might affect practice.
As this guideline applies to England and Scotland, the perspective was for both England and Scotland.
Objective tests for diagnosing asthma in adults, young people and children aged 5 to 16 with a history suggestive of asthma
Recommendations 1.2.1 to 1.2.9
Why the committee made the recommendations
Although evidence on symptoms and signs of asthma was not reviewed for this guideline update, the committee emphasised the importance of taking a good clinical history in all their discussions of diagnosis. Evidence on objective tests was only included if it was carried out in people in whom asthma was suspected on clinical grounds. Therefore, the recommendations for diagnostic testing should only be applied when the history and examination findings support a diagnosis of asthma. The committee also noted that, depending on the mode of presentation, other diagnoses might be considered, but they confined their recommendations to confirmation or exclusion of asthma.
The committee reviewed evidence on tests of variation in airflow obstruction and markers of allergy separately for adults and children. They took into account the sensitivity and specificity of the various tests but did not base their recommendations on these measures alone. They noted that no test showed high enough values of both sensitivity and specificity to be diagnostic in all cases. However, some of them showed high specificity and were potentially useful as rule-in tests with a suitably high cut-off value. It was agreed that a combination of tests would be needed for most people.
When considering combinations of tests, the extent to which the available tests correlate with one another is important because there is less benefit in performing a test that gives similar information to a preceding one. Practical aspects were taken into account using the committee's knowledge and experience. These included the availability of the tests, which varies considerably (in particular, bronchial challenge testing is not available in primary care and not readily available in secondary care), the ability of people to perform the tests, and the acceptability of the tests to the person, which is particularly relevant in younger children.
The committee also considered the cost of the available tests. However, no health economic study on the most cost-effective sequence or combination of tests was identified. Therefore, a health economic model was developed to help address this.
The committee discussed what cut-off values should be recommended for the tests. For some of the tests it was agreed that it was inappropriate to state a numerical value for an abnormal result. For example, normal ranges for blood tests may vary slightly between laboratories. Therefore, for eosinophil counts and IgE levels, a raised measurement (suggesting asthma) should be regarded as one above the upper end of the local reference range. There are also several standardised methods of performing bronchial challenge tests, and the definition of bronchial hyperresponsiveness will be dependent on the method used.
Spirometry should always be performed using an international standard protocol but the method of expressing reversibility after bronchodilator varies. Ideally this would be based on change in z-scores, but these are not measured by all spirometry equipment. Change in absolute values of FEV1 is arguably best given as the percentage change compared with the person's predicted FEV1, and using this parameter a change of 10% or more is abnormal. Using the more traditional means of expressing the change as a percentage of the baseline FEV1, increased reversibility would be 12% or more in adults and children. In adults, the change should also be 200 ml or more. The committee agreed to include both ways of measuring reversibility in its recommendations.
An optimal cut-off value is also difficult to give for FeNO (fractional exhaled nitric oxide). There is good evidence that FeNO levels increase with age and with height, and ideally normal ranges would be available which correct for these factors. However, there are currently no standard charts and FeNO equipment does not give an age/height corrected output. Although not ideal, the committee agreed that they need to suggest a simple cut-off value. And because FeNO is the first, and possibly the only, test in the recommended sequences in both adults and children they agreed that the value should be reasonably high so that it would be specific, acknowledging that this sacrifices a degree of sensitivity. Cut-offs of 50 ppb in adults and 35 ppb in children were agreed.
No evidence was available for diagnostic tests in children under 5. The age at which a child can co-operate with tests will vary, but the committee agreed that it is usually necessary to manage these children pragmatically based on symptoms and signs only.
Adults
Several tests showed good specificity for asthma, with values over 80% for blood eosinophils, FeNO (cut-off values 40-50 ppb), peak expiratory flow (PEF) variability, bronchial challenge tests, and spirometry with bronchodilator reversibility. However, sensitivity was poor for most of these, and only FeNO and bronchial challenge tests showed values over 70%. Although bronchial challenge is the most accurate test, overall, it is more costly than others and is less readily available.
Using the health economic model, the most cost-effective diagnostic strategy was found to be a gradual rule-in approach. It facilitates a positive diagnosis of asthma in a broad population using relatively inexpensive tests and confines the more expensive bronchial challenge tests to the end of the sequence.
The committee agreed that a cheap and highly specific test to rule in asthma should start the sequence. This should be either an eosinophil count or a FeNO measurement, but both need care in interpretation. For example, a raised eosinophil count can occur for other reasons including other allergic diseases, and FeNO is also affected by allergic diseases, although only those that affect the airways. Both measurements are altered in smokers. However, if used correctly in the presence of a history suggesting asthma, they are good rule-in tests.
The second test in the sequence should be to measure spirometry with reversibility. This is a more specific test than it is sensitive, but it represents a test of airway function to complement a first test which reflects atopy and so both components of asthma will have been assessed.
The committee were aware that there can be delays in accessing spirometry and FeNO testing, and it is hoped that access will improve. However, if these tests are not available or there is a significant delay in obtaining them, the committee agreed it would be reasonable to use PEF variability as a substitute rule-in test.
If asthma is not diagnosed at this stage, the only additional investigation that offers sensitivity without losing significant specificity is a bronchial challenge test. The committee are aware that these tests are not easily available in many areas but reasoned that making a positive recommendation should encourage services to improve access. They also noted that methacholine challenge is more sensitive than mannitol but did not want to further limit the recommendation.
Children aged 5 to 16
The committee noted that diagnostic testing is harder in children as they may find some tests difficult to perform and be unwilling to have blood tests.
A separate health economic model was developed for children using children-specific diagnostic accuracy data and inputs. In children, testing for sensitisation to house dust mite via skin prick test or finding an elevated IgE both showed high sensitivity. Therefore, the diagnostic strategy was a rule-in–rule-out approach. This proved to be the most cost-effective in children as it considerably reduced the proportion of children reaching the last stage and needing an expensive bronchial challenge test.
The committee agreed that a cheap and highly specific test was needed first to rule in asthma. FeNO is a more acceptable first test in children than an eosinophil count because it avoids the need to take blood, and because a level of 35 ppb or more is reasonably specific for asthma in the presence of a suggestive history.
The model suggested that a sensitive test should come next to rule out asthma. However, the committee noted that some children would not be able to have a FeNO test because the equipment is not available in all primary care settings, or because a minority may not be able to perform the necessary expiratory manouevre. They were also concerned that an increasing proportion of children with asthma are non-atopic and therefore unlikely to have a raised FeNO level. However, these children may show bronchodilator reversibility (BDR). It was therefore agreed that it would be appropriate to use spirometry with BDR as a second test for those without an elevated FeNO, or as the first test in those in whom FeNO could not be measured. Although this does not follow our optimal model exactly, including BDR at this stage is still cost-effective.
In children with a suggestive history of asthma, both skin prick testing for sensitisation to house dust mite and measurement of total IgE are sensitive tests, and the committee agreed that one or the other should be done next. If the test is negative, asthma is highly unlikely and can be ruled out without resorting to bronchial challenge testing. Although taking blood for IgE is invasive, it does have the advantage that an eosinophil count could also be obtained, and if this is above 0.5 x 109 per litre, it would support a diagnosis of asthma.
The committee were aware that there can be delays in obtaining spirometry, FeNO measurements or skin prick testing, and that it may not be possible to get blood samples from some children. It is hoped that access to these tests will improve. But if the tests are not available or there is a significant delay in obtaining them, the committee agreed it would be reasonable to use PEF variability as a substitute rule-in test.
The best single test is a bronchial challenge test, but these are also not readily available and cannot be done in primary care. If there is still diagnostic doubt after performing other tests, the committee agreed that a referral to an asthma specialist should be made for a second opinion, including consideration of a challenge test.
Further research
Although there is evidence underpinning each of the tests included in the recommended diagnostic sequences for adults and for children aged 5 to 16 years, the committee acknowledged that the sequences themselves have not been tested. The clinical and cost-effectiveness of the recommended diagnostic process should be formally evaluated.
Children under 5
The main issue in this age group is differentiating asthma from symptoms caused by recurrent viral infections. The committee were aware of evidence outside the review of diagnostic tests showing that asthma is more likely than recurrent viral wheeze when the episodes are frequent or severe, when they occur in the absence of other signs of viral illness and when the child shows other evidence of atopy. On this basis, they agreed that young children with recurrent wheeze and features suggesting asthma should be treated empirically with a low dose of inhaled corticosteroid (ICS) for a period of 8 to 12 weeks. If this is ineffective in reducing wheezing episodes, assuming that the ICS has been given satisfactorily, a referral to a specialist to consider other diagnoses is appropriate. If the ICS is associated with improvement, this is not proof of asthma as viral wheezing can remit and relapse spontaneously, so the committee agreed that the ICS should be stopped. If symptoms then reappear within a few weeks, asthma is the more likely diagnosis and the ICS should be re-started.
In view of the difficulty in diagnosing asthma in this age group the committee also agreed that any child who had been admitted to hospital, or been taken to the emergency department twice or more, because of wheezing or breathlessness should be referred to a specialist respiratory paediatrician for advice on diagnosis and management.
How the recommendations might affect practice
The diagnostic tests recommended for both children and adults are not routinely carried out in current practice, with the exception of spirometry and reversibility testing, which is performed in some adults with suspected asthma. FeNO equipment is not available in some areas, but an eosinophil count and IgE level is easily obtainable everywhere. Bronchial challenge tests are not done in primary care and infrequently used in secondary care. The recommendations will increase the demand for challenge tests and initially there will be a capacity problem. Incorporating the recommended diagnostic sequences into clinical practice would therefore require significant investment. However, using the tests increases the accuracy of asthma diagnosis and will be cost-effective over time.
The recommendations for children under 5 are based on a pragmatic trial of treatment, as is current practice.
Monitoring asthma control
Recommendations 1.5.1 to 1.5.4
Why the committee made the recommendations
The committee agreed that there is some information that should always be obtained at a routine monitoring review, for example whether any courses of oral corticosteroid have been needed since the last review.
Symptom questionnaires and diaries
The committee looked at evidence on the effects of monitoring asthma control using symptom questionnaires given at intervals ranging from weekly to twice in 3 months. Although there were a small number of beneficial outcomes in individual studies, overall, there was no clinically useful effect of the monitoring in either adults or children. The committee noted that the interventions were complex, as they assessed the effects not just of the symptom monitoring but also the therapeutic adjustments made in response to the questionnaire result. Nonetheless, they concluded that they should not recommend questionnaires used at these relatively frequent intervals.
The committee were aware of evidence (that was not part of this review) showing that the results of asthma control questionnaires predict the risk of future asthma attacks. They therefore used their experience to recommend that questionnaires should be used as part of any asthma-related review. For most people this will be their annual review.
Pulmonary function
The committee looked for evidence on the use of spirometry and PEF monitoring as measures of asthma control but did not find any data on spirometry used in this context.
There was evidence on PEF monitoring in both adults and children. The monitoring was typically linked to treatment changes triggered by designated thresholds of PEF and compared with the effects of treatment changes triggered by symptoms. In adults, regular PEF measurement was associated with worse quality-of-life parameters. The committee thought that this might be explained by regular monitoring inducing anxiety in some people if PEF is not consistently high, and by the inconvenience of making regular measurements.
In both adults and children, PEF monitoring was associated with an increase in asthma attacks, which appears to be a further disadvantage of regular monitoring. The committee found this hard to explain as monitoring itself seems unlikely to make asthma worse. It is possible that PEF measurements may have led to quicker identification and appropriate early treatment of some attacks. However, if this is the case, one might expect to see a reduction in the need for hospitalisation, or time off work or school, and these potential benefits were not seen.
The committee agreed that a minority of people with asthma benefit from regular measurement of PEF, for example those who are poor at perceiving changes in their airways and are therefore at risk of delaying treatment of asthma attacks. They also took into account evidence in adults that was not part of the formal review showing that action plans that incorporate PEF measurement can be beneficial. So, they recommended against the use of routine PEF monitoring, with the caveat that it might have value in some circumstances.
FeNO
The evidence showed that, in both adults and children, regular FeNO monitoring led to a reduction in the number of asthma exacerbations. In children there was also a significant improvement in lung function. In adults, the reduction in exacerbations was achieved alongside an overall reduction in the dosage of maintenance ICS therapy. This was not the case in children, but the studies in this age group were more likely to be conducted in secondary or tertiary care, so it is likely that they had a higher maintenance therapy requirement.
The committee concluded that FeNO monitoring was cost-effective in adults but may not be in children. It was not possible on the current evidence to say what the optimum frequency of monitoring should be, but the committee agreed that an appropriate opportunity would be to make a routine measurement at the person's regular review (which will be an annual review for most people).
The FeNO level is a proxy measure of airway inflammation. It can therefore be very useful in determining how to adjust treatment, or as an indicator of treatment adherence, when a person with asthma has poor symptom control. Conversely, when symptom control is excellent and the possibility of reducing maintenance therapy arises, a normal FeNO level provides helpful reassurance. The committee therefore agreed that a FeNO measurement should be considered whenever a change in maintenance therapy might be appropriate.
How the recommendations might affect practice
Asthma control questionnaires are already recommended as part of an annual review. Therefore, no change to practice is anticipated. The recommendations on pulmonary function are expected to reduce the use of PEF monitoring.
Measurement of FeNO is increasingly used in secondary care asthma clinics, but in primary care only a minority of GP practices have on-site access to the test. Regular FeNO monitoring represents a significant change in practice because most people with asthma are managed in primary care. This change will also carry a cost. The committee noted that FeNO measurement is also useful in diagnosing asthma (see section 1.2 on objective tests for diagnosing asthma), and increased access to the test will therefore be of dual benefit.
Principles of pharmacological treatment
Recommendations 1.6.2 and 1.6.3
Why the committee made the recommendations
The evidence review showed that clinical outcomes were poorest in all age groups with asthma when using SABA (short-acting beta2 agonist) alone. The committee also took into account other evidence from several sources, including national reviews of asthma deaths in both adults and children, which highlighted the dangers of using SABA without ICS in people with asthma. They therefore recommended that SABA alone should not be used in people with a diagnosis of asthma.
The previous NICE and BTS/SIGN guidelines had recommended a number of actions which should be taken before increasing treatment, and the committee agreed by consensus that a FeNO check should also be done as long as the equipment is available to do this.
How the recommendations might affect practice
The prescription of SABA alone has been commonplace, although this is becoming less so because of the publicity around asthma deaths. The recommendation will reduce its use further. The replacement therapies in adults and children are more expensive, but they should produce clinical benefits and cost savings through a reduction in exacerbations.
Digital inhalers
Why the committee made the recommendation
The committee looked at evidence comparing the use of digital smart inhalers with usual care and with digital inhalers with the feedback utility switched off. The trials included both children and adults with asthma, and a variety of types of inhaler. The evidence showed improvement in adherence to treatment with digital inhalers, but this did not result in significant improvement in measures of asthma control. In addition, there was an unexplained increase in hospital admissions among people using digital inhalers when compared with usual care. The participants in the contributing trials varied considerably in terms of baseline adherence and asthma control, and benefit was generally more likely in the studies of people with poorer baseline values.
Digital inhalers are more expensive than conventional devices, partly because of the device itself and partly because of the set-up and monitoring requirements. The committee concluded that digital inhalers are not a cost-effective option for routine use in asthma. However, they are potentially valuable in selected people with asthma, for example those in whom the need for biologic therapy is being considered and there is a need to confirm good adherence. Further research is needed to identify more precisely the people and the circumstances in which they might be used.
How the recommendation might affect practice
Digital inhalers are not recommended for routine use in the NHS, and this is in line with current practice.
Medicines for the initial management of newly diagnosed asthma in people aged 12 and over
Recommendations 1.7.1 and 1.7.2
Why the committee made the recommendations
The committee looked at evidence comparing 3 treatment options in people aged 12 and over with a new diagnosis of asthma. These were SABA as needed with no ICS; regular low-dose ICS plus SABA as needed; and a combination inhaler of an ICS (budesonide) plus formoterol, a fast onset long-acting beta2 agonist (LABA), used as needed (as-needed AIR).
The most important difference between the groups was a reduction in severe exacerbations of asthma in the group using as-needed AIR therapy, and this applied to the comparisons with both of the other treatment options. There were also fewer exacerbations with ICS plus SABA than with SABA alone. Apart from the difference in exacerbations, there were only small differences between outcomes when comparing ICS plus SABA as needed with as-needed AIR, and the committee did not assess these as clinically important. However, the evidence showed that use of ICS (either as-needed AIR or regular low-dose ICS plus SABA as needed) produced consistently better outcomes than SABA alone.
Health economic data showed that treatment with as-needed AIR was cheaper than regular ICS plus SABA as needed. The committee therefore concluded that combination inhalers used as needed should be the preferred treatment in newly diagnosed asthma in adults. However, there were concerns about the minority of people with asthma in whom the diagnosis is first made because of an acute attack. In these particularly symptomatic people, the committee agreed on safety grounds that initial treatment should be given regularly and recommended starting the low-dose MART (maintenance and reliever therapy) regimen.
How the recommendations might affect practice
Most people aged 12 and over with newly diagnosed asthma are currently treated with either a SABA alone or with regular ICS plus SABA as needed. The new recommendations represent a significant change in practice. The use of combination inhalers is more expensive than SABA alone, but cheaper than regular ICS plus SABA as needed. Therefore, the cost impact will vary depending on the predominant form of treatment in each general practice. However, there should be future savings from a reduction in severe asthma exacerbations compared with either of the current treatment options.
Medicine combination and sequencing in people aged 12 and over
Recommendations 1.7.3 to 1.7.6
Why the committee made the recommendations
No studies were found in which treatment was added to as-needed AIR, the recommended first treatment step in people aged 12 and over. This was unsurprising as the advantages of this as initial therapy have only recently been recognised. The committee therefore had to consider studies of people with asthma uncontrolled on other starting treatments, either a SABA when used as needed as sole therapy or when used in addition to regular low-dose ICS. They reasoned that these people would be sufficiently similar to people who are not controlled with as-needed AIR to allow recommendations to be made, but agreed that further research comparing different add-on therapies to ICS/formoterol as needed would be useful.
The evidence showed that regular low-dose ICS/LABA plus SABA as needed was superior to regular low-dose ICS plus SABA as needed. It produced greater improvements in lung function, and a reduction in the number of exacerbations and the amount of reliever therapy needed. Low-dose MART was also better than regular low-dose ICS plus SABA as needed in reducing asthma exacerbations, and people on this treatment needed less reliever therapy.
When low-dose ICS/LABA plus SABA as needed was compared with low-dose MART, the people using MART were found to have fewer exacerbations and hospital admissions. The committee noted that it would be simpler for people who are already using an ICS/formoterol inhaler to start the MART regimen than to convert to new inhalers. The committee also considered the economic analysis done for this update and agreed that the MART regimen would be a cost-effective use of resources compared with low-dose ICS/LABA plus SABA as needed.
If treatment with MART using a low-dose maintenance regimen does not provide adequate asthma control, the committee agreed that increasing the maintenance element of MART to moderate dose is the appropriate next step. Evidence supporting this was available from studies comparing moderate dose MART with both regular moderate dose ICS/LABA with SABA as reliever and with regular moderate dose ICS with SABA as reliever. MART was superior in both comparisons, most notably in reducing severe asthma exacerbations.
If treatment with MART using a moderate-dose maintenance regimen does not provide adequate asthma control, the evidence on how best to increase treatment is less clear cut. People whose asthma is uncontrolled at this stage will be using additional doses of ICS/formoterol for symptom relief and will effectively be on high-dose ICS. The committee agreed that ideally both FeNO and the eosinophil level should be checked, as well as carefully assessing whether the person is adhering to their prescribed treatment. If FeNO or eosinophil count is raised despite good adherence to this level of ICS, the risk of adverse outcomes is relatively high and a referral to an asthma specialist for further assessment and management is appropriate.
If control is inadequate but neither FeNO nor eosinophil count is raised, the committee considered the possible options to be the addition of either a leukotriene receptor antagonist (LTRA) or a long-acting muscarinic receptor antagonist (LAMA). Evidence was available looking at the addition of either an LTRA or a LAMA to baseline treatment with moderate-dose ICS or moderate-dose ICS/LABA, but the 2 options were only compared directly in 2 small studies. Although the comparison showed a reduction in exacerbations with a LAMA compared with an LTRA, the committee did not have much confidence in the result because of the small study population. They noted that it would be simpler to add an LTRA than a LAMA because the latter would involve needing to teach the person with asthma how to use an additional inhaler device, and the need for 2 inhalers is also less environmentally desirable. An LTRA is also cheaper, but there is a risk of significant side effects, particularly neuropsychiatric disturbances. It was agreed that there was no convincing reason to recommend one option over the other and that the person with asthma should decide which should be tried first after a discussion of the potential benefits and harms.
If these medicines have been tried and the person's asthma continues to be inadequately controlled, further treatment is available using a variety of biologic agents. Use of these falls outside the scope of this guideline and requires specialist assessment. The committee therefore recommended that a referral should be made at this stage.
How the recommendations might affect practice
The recommendations for increasing treatment are different from current standard practice, but they apply to people with a new diagnosis of asthma. People with an existing diagnosis of asthma who are stable on their current therapy do not have to switch treatment. People on current pathways who need an increase in treatment will be switched to MART, but this is one of the current options. There should therefore not be significant disruption to asthma care. The new treatment steps are cost-effective for the NHS and in particular will reduce the number of exacerbations requiring treatment and the number of hospital admissions for asthma.
Transferring people aged 12 and over from other treatment pathways
Recommendations 1.7.7 to 1.7.11
Why the committee made the recommendations
The treatment pathway recommended in this guideline update for people aged 12 and over relies on using MART with increasing dose of regular ICS/formoterol, depending on response to treatment. This is a different strategy from that recommended by previous guidelines (NICE and BTS/SIGN) and many people will be on treatment that is not part of this new pathway. The committee recognised that this will cause a problem for these people when their asthma is not controlled. They therefore discussed and agreed how treatment should be changed in these circumstances. They noted that the general advice about checking inhaler technique, adherence, etc. (see recommendation 1.6.1 in the section on principles of pharmacological treatment) before escalating treatment still applies here. The recommendations are not based on a specific evidence search, but the committee noted that people in the MART studies reviewed for recommendations 1.7.3 to 1.7.6 (see the section on medicine combination and sequencing in people aged 12 and over) were taking some form of non-MART therapy before study entry and that the improvement shown in comparison to both baseline and to the control treatments support the switch to MART.
How the recommendations might affect practice
The recommendations will result in more people being switched to MART than to other treatment options, but MART is used at present, and the change should not be disruptive.
Medicines for initial management in children aged 5 to 11
Why the committee made the recommendation
Evidence for children aged 5 to 11 showed that regular paediatric low-dose ICS plus SABA as needed was superior to SABA alone, particularly in reducing exacerbations. Using regular ICS did not cause more side effects and was not associated with greater adrenal suppression. There was no evidence for ICS/formoterol combination inhalers used as needed in this age group. The committee therefore recommended regular paediatric low-dose ICS as the preferred treatment option for children aged 5 to 11. However, in view of the evidence supporting the use of ICS/LABA as needed combination inhalers in adults, they made a research recommendation to test the benefits of this combination in children.
How the recommendation might affect practice
The recommendation for treatment of newly diagnosed asthma in children is in line with current practice.
Medicine combination and sequencing in children aged 5 to 11
Recommendations 1.8.2 to 1.8.7
Why the committee made the recommendations
The committee recommended regular low-dose ICS plus SABA as needed as initial treatment for children diagnosed with asthma. Several studies were available which directly addressed the question of optimal add-on therapy for children whose asthma is not controlled on this treatment. This evidence for MART was from a single study which showed that MART was superior to both regular moderate-dose ICS plus SABA as needed and to regular low-dose ICS/LABA plus SABA as needed. It reduced the number of exacerbations, reduced the need for reliever inhaler and caused fewer adverse events. The economic analysis done for this guideline update also supported the clinical evidence and the committee's discussion, with the MART regimen associated with fewer costs and more quality-adjusted life years (QALYs) than both ICS/LABA plus SABA as needed and ICS plus SABA as needed.
The results for the comparison of regular low-to-moderate dose ICS plus SABA as needed with regular low-dose ICS/LABA plus SABA as needed were equivocal, with fewer exacerbations on regular treatment with low-to-moderate dose ICS but more hospital admissions.
The committee agreed that paediatric low-dose MART is the best treatment for a child whose asthma is uncontrolled on regular paediatric low-dose ICS. They noted that MART is currently not licensed in the UK below the age of 12, although the key study recruited children younger than this, with a minimum age of 4. In addition, there were concerns that some children might struggle to use a dry-powder inhaler when particularly breathless. The committee therefore agreed to recommend MART as the preferred treatment providing the child is able to manage the MART regimen and the healthcare professional is willing to prescribe it.
For children whose asthma is uncontrolled on regular paediatric low-dose ICS and who are unable to manage the MART regimen, the choice of treatment would be between adding an LTRA, adding a LABA, or increasing the maintenance ICS dose. The evidence did not show one option to be clearly superior in terms of benefits or adverse events, although the committee noted that prescribers should warn people of possible neuropsychiatric problems with montelukast. (See the MHRA drug safety update on the risk of neuropsychiatric reactions in people taking montelukast.) The committee agreed that adding an LTRA to the regular ICS treatment should be tried first as this limits the child's exposure to ICS and is less expensive than using ICS/LABA inhalers. They used their knowledge and expertise to recommend further steps if asthma control is not achieved.
The committee also agreed that if asthma control was not achieved on a regular moderate dose of ICS (either as paediatric moderate-dose MART or regular paediatric moderate-dose ICS/LABA plus SABA as needed), an opinion should be sought from a specialist in asthma care before escalating to a paediatric high-dose ICS regimen.
How the recommendations might affect practice
The recommendation for MART as the preferred step-up treatment is new, but this is not intended for children who are stable on current therapy, and introducing it should not be disruptive. It will bring advantages in terms of reducing asthma attacks. In addition, MART will not be suitable for some children, and the recommendations for treatment in this group are in line with current practice. Overall, the changes are modest and will be cost-effective for the NHS.
Pharmacological management in children under 5
Recommendations 1.9.1 to 1.9.6
Why the committee made the recommendations
Evidence was available for 5 treatment options: SABA alone used as needed; regular ICS plus SABA as needed; SABA/ICS combination inhaler used as needed; regular SABA/ICS combination inhaler; and regular montelukast. The evidence did not encompass all possible comparisons of the 5 options, but overall, those that included the use of an ICS clearly showed greater benefits than those without an ICS, and regular ICS (either ICS alone or ICS/SABA) was superior to intermittent ICS/SABA. The most important benefits of regular ICS were seen in reducing exacerbations or hospital admissions. There was no advantage to using regular ICS/SABA instead of regular ICS alone.
In making recommendations for this age group, the committee took into account the difficulty of making a firm diagnosis of asthma. Episodes of cough and wheezing can occur with recurrent viral infections and be difficult to distinguish from asthma, and there are concerns about treating young children with long-term ICS when they may not need them.
The committee were aware of evidence outside the review of diagnostic tests showing that asthma is more likely than recurrent viral wheeze when the episodes are frequent or severe, when they occur in the absence of other signs of viral illness and when the child shows other evidence of atopy. They made recommendations on the staged introduction of ICS as part of the diagnostic process in infants. They agreed that young children with recurrent wheeze and features suggesting asthma should be treated empirically with a low dose of ICS for 8 to 12 weeks, and then this can be stopped. If symptoms soon re-appear after stopping ICS, this suggests that the ICS was beneficial rather than the improvement being due to the natural remission of a viral episode. Once the presence of asthma is established with reasonable certainty the committee agreed that regular paediatric low-dose ICS should be restarted, with subsequent steps added if needed.
As diagnosis in this age group is so difficult, the committee agreed that thresholds for referral to an asthma specialist should be low.
How the recommendations might affect practice
The recommendations for treatment of newly diagnosed asthma in children are in line with current NICE recommendations.
Self-management
Why the committee made the recommendation
The evidence for children and young people found that increasing the dose of ICS when asthma control deteriorates did not result in any benefits or harms compared with the usual dose in terms of reducing subsequent asthma exacerbations. It was limited to only 1 study with a small number of participants who had a personalised action plan. The committee also looked at studies in adults, but they agreed that the evidence was not applicable because of the high average age of participants.
The committee discussed the importance of a personalised action plan to guide children and young people if their asthma worsens and to reassure them that they are in control of their treatment. Children and young people who find that increasing their dose of ICS is helpful when their asthma control worsens should be able to continue to do this as an agreed strategy in their action plan. However, based on their experience, the committee members agreed that it is important to review the child or young person's self-management plan if their asthma control is deteriorating. Reviews involve checking current medicines and inhaler technique, discussing any factors that may be triggering symptoms, discussing adherence and education needs, and reviewing their action plan. They should be carried out as needed, in addition to annual review.
The committee discussed the importance of an individualised approach for children and young people, because they have varied and changing support needs at different ages. Studies have shown that most child asthma deaths involve children who have frequent but mild symptoms that are not responding to management in their personalised action plan. This recommendation should help to ensure that these children and young people receive the support that they need if they start to have problems with their asthma control.
The committee agreed that further research is needed to give clearer guidance on increasing the dose of ICS in children and young people within a self-management programme. They made a research recommendation on increasing the dose of ICS within a personalised self-management programme for children and young people to promote further research and inform future practice.
How the recommendation might affect practice
The recommendation will lead to an increase in the review of self-management programmes for children and young people and reduce the variation in current practice for this. The increase in resources needed for this is likely to be offset by a reduction in the cost of treating asthma exacerbations.
Risk-stratified care
Why the committee made the recommendation
The studies featured differing ways of attempting to improve asthma care for people judged to be at high risk of adverse outcomes. Therefore, firm conclusions on the overall benefits were hard to reach. In addition, the factors used to identify the high-risk population were not identical across the different studies. The committee therefore were unable to define precisely how to identify people at risk, although they agreed that poor prescription pick-up rates, overuse of SABA inhalers and previous exacerbations needing unscheduled medical care are very likely to be relevant.
Most of the studies showed some reduction in A&E attendance or hospitalisation after risk stratification. The committee particularly noted 2 UK studies in which at-risk patients were identified by alerts on GP computer systems. These indicated that risk-stratified care helped healthcare professionals to better identify people who needed a course of oral corticosteroids. This then successfully reduced the number of hospitalisations and the need for out-of-hours contacts and A&E attendance for asthma exacerbations. An associated health economic review showed that risk stratification is likely to be cost-effective.
Based on this evidence and their clinical experience, the committee agreed there should be a benefit in identifying people 'at risk' of poor asthma outcomes and recommended that primary care services should consider introducing a risk-stratification system which then allows care to be adjusted according to the greater needs of some people.
How the recommendation might affect practice
Many general practices have some form of alert system in operation already, but others do not. For those, the recommendation will result in a change in practice. The committee were uncertain how many different systems are in current use, but in the absence of comparative data, they could not recommend that some practices would need to change from their current system.