| Context | Recommendation | Strength | Quality of evidence | Values and preferences | Remarks | |
| Computed tomography of chest | 1 | In children and adults with severe asthma without specific indications for chest HRCT based on history, symptoms and/or results of prior investigations we suggest that a chest HRCT only be done when the presentation is atypical | Conditional | Very low | This recommendation places a relatively high value on identification of alternative diagnosis and comorbidities and a relatively low value on avoiding potential complications and cost of chest HRCT | An atypical presentation of severe asthma includes such factors as, for example, excessive mucus production, rapid decline in lung function, reduced carbon monoxide transfer factor coefficient and the absence of atopy in a child with difficult asthma |
| Sputum eosinophil counts | 2A | In adults with severe asthma: we suggest treatment guided by clinical criteria and sputum eosinophil counts performed in centres experienced in using this technique rather than by clinical criteria alone | Conditional | Very low | The recommendation to use sputum eosinophil counts to guide therapy in adults places a higher value on possible clinical benefits from adjusting the treatment in selected patients and on avoidance of inappropriate escalation of treatment and a lower value on increased use of resources | Because, at the present time, measurement of sputum eosinophils has not yet been sufficiently standardised and is not widely available we suggest such an approach be used only in specialised centres experienced in this technique. Patients who are likely to benefit from this approach are those who can produce sputum, demonstrate persistent or at least intermittent eosinophilia and have severe asthma with frequent exacerbations Clinicians should recognise that different choices will be appropriate for different patients |
| 2B | In children with severe asthma: we suggest treatment guided by clinical criteria alone rather than by clinical criteria and sputum eosinophil counts | Conditional | Very low | The recommendation not to use sputum eosinophil counts to guide therapy in children places higher value on avoiding an intervention that is not standardised and not widely available and lower value on the uncertain and possibly limited clinical benefit | ||
| Exhaled nitric oxide | 3 | We suggest that clinicians do not use FeNO to guide therapy in adults or children with severe asthma | Conditional | Very low | This recommendation places a higher value on avoiding additional resource expenditure and a lower value on uncertain benefit from monitoring FeNO | |
| Anti-IgE antibody (omalizumab) | 4 | In patients with severe allergic asthma we suggest a therapeutic trial of omalizumab both in adults and in children | Conditional | Low (adults) Very low (children) | This recommendation places higher value on the clinical benefits from omalizumab in some patients with severe allergic asthma and lower value on increased resource use | Those adults and children aged ≥6 years with severe asthma who are considered for a trial of omalizumab, should have confirmed IgE-dependent allergic asthma uncontrolled despite optimal pharmacological and non-pharmacological management and appropriate allergen avoidance if their total serum IgE level is 30–700 IU·mL−1 (in three studies the range was wider: 30–1300 IU·mL−1) Treatment response should be globally assessed by the treating physician taking into consideration any improvement in asthma control, reduction in exacerbations and unscheduled healthcare utilisation, and improvement in quality of life If a patient does not respond within 4 months of initiating treatment, it is unlikely that further administration of omalizumab will be beneficial |
| Methotrexate | 5 | We suggest that clinicians do not use methotrexate in adults or children with severe asthma | Conditional | Low | This recommendation places a relatively higher value on avoiding adverse effects of methotrexate and a relatively lower value on possible benefits from reducing the dose of systemic corticosteroids | Evidence from randomised trials is only available for adults Because of the probable adverse effects of methotrexate and need for monitoring therapy we suggest that any use of methotrexate is limited to specialised centres and only in patients who require daily OCS If a decision to use methotrexate is made chest radiography, complete blood count with differential and platelets, liver function tests, serum creatinine and DLCO are recommended prior to and after commencing therapy |
| Macrolide antibiotics | 6 | We suggest that clinicians do not use macrolide antibiotics in adults and children with severe asthma for the treatment of asthma | Conditional | Very low | This recommendation places a relatively higher value on prevention of development of resistance to macrolide antibiotics, and relatively lower value on uncertain clinical benefits | This recommendation applies only to the treatment of asthma; it does not apply to the use of macrolide antibiotics for other indications, e.g. treatment of bronchitis, sinusitis or other bacterial infections as indicated |
| Antifungal agents | 7A | We suggest antifungal agents in adults with severe asthma and recurrent exacerbations of ABPA | Conditional | Very low | The recommendation to use antifungal agents in patients with severe asthma and ABPA places a higher value on possible reduction of the risk of exacerbations and improved symptoms, and a lower value on avoiding possible adverse effects, drug interactions and increased use of resources | In children, the evidence is limited to isolated case reports Children should be treated with antifungals only after the most detailed evaluation in a specialist severe asthma referral centre As antifungal therapies are associated with significant and sometimes severe side-effects, including hepatotoxicity, clinicians should be familiar with these drugs and follow relevant precautions in monitoring for these side-effects, observing the limits to the duration of treatment recommended for each |
| 7B | We suggest that clinicians do not use antifungal agents for the treatment of asthma in adults and children with severe asthma without ABPA irrespective of sensitisation to fungi (i.e. positive skin prick test or fungus-specific IgE in serum) | Conditional | Very low | The recommendation not to use antifungal agents in patients with severe asthma without confirmed ABPA (irrespective of sensitisation) places a higher value on avoiding possible adverse effects, interactions of antifungal agents with other medications and increased use of resources, and a lower value on uncertain possible benefits | The recommendation not to use antifungal agents in patients with severe asthma without confirmed ABPA applies only to the treatment of asthma; it does not apply to the use of antifungal agents for other indications, e.g. treatment of invasive fungal infections | |
| Bronchial thermoplasty | 8 | We recommend that bronchial thermoplasty is performed in adults with severe asthma only in the context of an Institutional Review Board approved independent systematic registry or a clinical study (recommendation, quality evidence) | Strong | Very low | This recommendation places a higher value on avoiding adverse effects, on an increased use of resources, and on a lack of understanding of which patients may benefit, and a lower value on the uncertain improvement in symptoms and quality of life | This is a strong recommendation, because of the very low confidence in the currently available estimates of effects of bronchial thermoplasty in patients with severe asthma Both potential benefits and harms may be large and the long-term consequences of this new approach to asthma therapy utilising an invasive physical intervention are unknown Specifically designed studies are needed to define its effects on relevant objective primary outcomes, such as exacerbation rates, and on long-term effects on lung function Studies are also needed to better understand the phenotypes of responding patients, its effects in patients with severe obstructive asthma (FEV1 <60% of predicted value) or in whom systemic corticosteroids are used, and its long-term benefits and safety Further research is likely to have an important impact on this recommendation |
HRCT: high-resolution computed tomography; FeNO: exhaled nitric oxide fraction; OCS: oral corticosteroids; DLCO: transfer factor of the lung for carbon monoxide; ABPA: allergic bronchopulmonary aspergillosis; FEV1: forced expiratory volume in 1 s.