* Strength of recommendation/Quality of evidence
Management of stable asthma
REC 1: In order to determine the best management approach, asthma control should be assessed using severity and frequency of symptoms. (Particularly nocturnal symptoms, exercise induced wheezing, the use of beta agonists and absence from work/school due to symptoms, the frequency of exacerbations and peak expiratory flow (PEF) if available.)
* (Strong recommendation, low quality evidence) Annex 4.1; 4.2
REC 2: Inhaled corticosteroids (beclometasone) should be given to all patients with chronic persistent asthma. If their use needs to be prioritized in resource-constrained settings, the highest priority group should be those with life-threatening attacks and attacks requiring hospital admission where the use of a regular inhaled steroid is likely to save money by reducing hospital admissions. Patients with frequent exacerbations are also a high priority group, as are those with persistent troublesome symptoms, those using high doses of beta agonists and those losing time from work or school.
Numerous studies have demonstrated that inhaled steroids reduce asthma exacerbations and improve lung function, although they vary in terms of dosage used, type of steroid and mode of delivery, including the use of a spacer. Low doses (e.g. beclometasone 100ug once or twice daily for children and 100ug or 200ug twice daily for adults) are adequate for most patients with mild or moderate asthma; patients with more severe asthma require higher doses.
The lowest dose of beclometasone that controls symptoms should be determined for maintenance treatment. Any deterioration in symptom control should be treated with an increase in dose. A spacer should be used with a metered-dose inhaler (MDI) to reduce candidiasis and increase drug deposition in the lung.
Ensuring that low-cost, good quality generic preparations of inhaled beclometasone are readily available for all patients with persistent asthma is the highest priority.
* (Strong recommendation, moderate quality evidence) Annex 4.3; 4.4
REC 3: A stepwise approach to treatment is recommended:
Step 1. Inhaled beta agonist (salbutamol) as required (prn)
Step 2. Continue inhaled salbutamol prn and add inhaled beclometasone 100ug or 200ug twice daily, or 100ug once or twice daily in children
Step 3. Continue inhaled salbutamol prn and increase the dose of beclometasone to 200ug to 400ug twice daily
Step 4. Add low-dose oral theophylline (assuming that long-acting beta agonists are not available), or increase dose of inhaled beclometasone
Step 5. Add oral prednisolone in the lowest dose possible to control symptoms
At each point it is important to check patients' adherence to their medications and that their inhaler technique is correct. For patients requiring regular prednisolone referral to a specialised centre should be considered.
* Annex 7
Management of exacerbation of asthma
REC 1: Oral prednisolone should be given for all acute exacerbations of asthma. For adults, a dose of 30–40mg daily is appropriate, while for children (<16 years) a dose of 1mg per kg daily has fewer adverse effects on behaviour than 2mg per kg, so a dose of 1mg per kg (up to 30mg daily) is recommended. Patients should have easy access to oral corticosteroids for exacerbations. In children, prednisolone tablets can be crushed and given with sugar. The usual duration of treatment is three days for children and five days for adults though it may need to be extended if the patient has not recovered fully.
* (Strong recommendation, low-quality evidence) Annex 4.6
REC 2: Inhaled salbutamol: higher doses of inhaled salbutamol should be given to all patients with acute severe exacerbations; salbutamol may be given by nebulizers or spacers (commercial or homemade). The evidence suggests no important advantages of nebulizers over spacers in children over the age of 2 (or adults) although these studies did not include patients with life-threatening asthma. Other considerations may be relevant in making the choice between nebulizers and spacers such as the availability of nebulizers, the need to prevent cross-infection and whether the patient will use a spacer at home. Steps must be taken to keep nebulizers and spacers clean (sterile) and to prevent transmission of infections.
Following treatment with salbutamol, patients should have repeat clinical assessments at intervals (e.g. 15–20 minute intervals) to ensure that they are responding to treatment. Failure to respond requires further doses or more intensive treatment.
Once the patients have recovered, their usual maintenance treatment should be reviewed and altered if indicated to prevent recurrent exacerbations.
* (Strong recommendation, low-quality evidence) Annex 4.7; 4.8; 4.15
REC 3: Oxygen: if available, oxygen should be administered to patients with acute severe asthma. This is in keeping with normal practice in high-resource settings where the decision to use oxygen is based on low oxygen saturation readings.
* (Strong recommendation, very low-quality evidence)
REC 4: Second-line drugs: if patients do not respond to salbutamol and prednisolone, then second-line drugs may need to be considered. If a nebulizer and ipratropium bromide are available and a second-line treatment is required, nebulized ipratropium bromide is recommended for children with acute asthma.
* (Weak recommendation, very low-quality evidence)
REC 5: Intravenous magnesium: at present, there is insufficient evidence to recommend intravenous magnesium as a routine second-line drug.
* (Weak recommendation, very low-quality evidence)
REC 6: Intravenous salbutamol: on the basis of the balance between benefits and risks, intravenous salbutamol is NOT recommended for use as a second-line drug.
* (Strong recommendation, very low-quality evidence)
REC 7: Intravenous aminophylline: on the basis of the balance between benefits and risks, intravenous aminophylline is NOT recommended for routine use as a second-line drug. When taken in addition to beta agonists and steroids there is no significant benefit for adults and only marginal benefit for children. There is evidence of adverse effects for children and adults. The risks are seen as outweighing the benefits in settings where monitoring is not feasible.
* (Weak recommendation, very low-quality evidence)
Management of stable COPD
REC 1: When given as required short-acting beta-agonists are effective in improving symptoms in patients with stable COPD. Patients should be prescribed beta agonists as required. There are no data from which to assess the optimum frequency of administration, or the effect of regular administration. Inhaled beta agonists are recommended rather than oral preparations because oral preparations have more pronounced undesirable effects that may be of particular relevance in view of common co-morbidities with COPD, e.g. arrhythmias in patients with coronary heart disease.
* (Weak recommendation, very low-quality evidence) Annex 4.11; 4.12
REC 2: Theophylline: as it is unlikely that blood levels can be monitored in resource-constrained settings, only low doses of theophylline are recommended. Patients should be advised to stop treatment and consult a doctor if adverse effects are experienced.
* (Weak recommendation, very low-quality evidence) Annex 4.14
REC 3: Oral corticosteroids (prednisolone) are ineffective in stable COPD except possibly in high doses when there are important side effects. On the basis of the balance between benefits and risks, oral steroids are NOT recommended for use in stable COPD.
* (Strong recommendation, very low-quality evidence) Annex 4.13
REC 4: Inhaled steroids (beclometasone): when given in high doses there may be a small benefit from inhaled steroids; however, high doses are expensive for resource-poor countries and high doses have more adverse effects, including pneumonia. The risks are unknown in areas where the prevalence of HIV and tuberculosis are high. Since the benefit is modest, the risk/benefit ratio is much higher than it is for asthma. The use of inhaled steroids for patients with stable COPD therefore cannot be justified. NOT recommended.
* (Strong recommendation, very low-quality evidence)
REC 5: Ipratropium bromide: when compared to regular short-acting beta agonists, short-term inhaled ipratropium bromide has small benefits with regard to reducing symptoms and improving lung function. Currently, ipratropium bromide preparations are more expensive than beta agonists and there are no data to assess risk versus benefits of regular use over longer periods to recommend long-term regular use of ipratropium bromide. NOT recommended.
* (Weak recommendation, very low-quality evidence) Annex 4.12
Management of exacerbation of COPD
REC 1: Antibiotics should be given for COPD exacerbations.
* (Strong recommendation, very low-quality evidence) Annex 4.10
REC 2: Oral steroids: a short course of prednisolone is recommended for acute severe exacerbations of COPD (e.g. prednisolone 30–40mg for about seven days).
* (Strong recommendation, very low-quality evidence) Annex 4.14
REC 3: Inhaled beta agonists: higher doses of inhaled salbutamol should be administered via a nebulizer or spacer.
* (Strong recommendation, very low-quality evidence) Annex 4.12
REC 4: Oxygen: if available, oxygen should be administered by a device that controls concentration to 24%–28%.
* (Strong recommendation, very low-quality evidence)
REC 5: Intravenous aminophylline: based on the available evidence, intravenous aminophylline is NOT recommended for routine use in acute exacerbations of COPD. Although there are data from only four studies, these show little evidence of benefit; any beneficial effect is likely to be small and is likely to be outweighed by potential adverse effects.
* (Strong recommendation, very low-quality evidence)
The summaries of the considerations of benefits/risks, values, cost and feasibility for the recommendations listed in the following table were discussed by the guideline expert panel based on the experience of its members, consideration of the systematic reviews, moderated discussion and consensus.
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| Recommendation | Benefits/risks; values and acceptability; cost; feasibility |
|---|
| Management of stable asthma |
|---|
| REC 1 | Standard diagnostic recommendations to assess asthma control should be used in accordance with standard clinical practices, as agreed by the guideline expert panel members. |
| REC 2 | Benefits:
Highly effective treatment for control of stable asthma as well as significant reduction of exacerbations and improvement of lung function.
Risks:
Risks of side effects are minimal since only the lowest dose that controls symptoms is recommended for maintenance treatment. A spacer should be used with an MDI to reduce candidiasis with beclometasone and increase drug deposition in the lung.
Values and acceptability:
Numerous studies have demonstrated that inhaled steroids reduce asthma exacerbations and improve lung function, although they vary in terms of dosage used, type of steroid and mode of delivery, including the use of a spacer.
Cost:
The regular use of inhaled steroids is likely to save money by reducing hospital admissions of patients with life-threatening attacks and frequent exacerbations. Low-cost, good quality generic preparations of inhaled steroids are recommended.
Feasibility:
Particularly recommended in resource-constrained settings where access to medical care is often restricted. |
| REC 3 | A stepwise approach is a commonly accepted way of managing asthma patients and basically comprises all the other treatment recommendations, as agreed by the guideline expert panel members. |
| Management of exacerbation of asthma |
|---|
| REC 1 | Benefits/risks:
Benefits far outweigh the risks. For all acute exacerbations of asthma, short-term courses of oral steroids in the recommended doses are effective and carry minimal risk of side effects, e.g. weight gain, fluid retention, high blood pressure, elevated blood sugar.
Values and acceptability:
The efficiency in acute exacerbations of asthma is demonstrated in numerous studies. In the recommended doses, a significant benefit is derived with little risk of side effects.
Cost:
Affordable for resource-constrained settings.
Feasibility:
There should be easy access to oral corticosteroids for patients with exacerbations of asthma. |
| REC 2 | Benefits/risks:
Effective for improving lung function in patients with acute exacerbations of asthma. For short-term administration of high doses, benefits outweigh the risk of potential side effects. Generally, the evidence suggests no important advantages of nebulizers over spacers.
Values and acceptability:
Based on the severity of asthma exacerbations, prompt treatment can be vital. Following treatment with salbutamol, the patient should have repeated clinical assessments at intervals (e.g. 15–20 minute intervals) to ensure that they are responding to treatment. Failure to respond requires further doses or more intensive treatment.
Cost:
There are no data available directly assessing the cost effectiveness, although, the cost is lower where good quality generic preparations are available.
Feasibility:
Higher doses of inhaled beta agonists should be given to all patients with acute severe exacerbations where available. |
| REC 3 | Benefits/risks:
In the absence of evidence from randomized controlled trials (RCTs) in asthma, the recommendation is based on observational evidence and strong consensus belief that oxygen is beneficial.
Values and acceptability:
If oxygen is available, it should be administered to all patients with acute severe asthma in keeping with normal practice in high-resource settings where the decision to use oxygen is based on low oxygen saturation readings (pulse oximetry).
Cost:
Short-term use in exacerbations as recommended should be affordable. |
| REC 4 | If a nebulizer and ipratropium bromide are available and a second-line treatment is required, adding ipratropium bromide can be recommended for children with acute asthma but ONLY as a second-line treatment. Side effects are rare; paradoxical bronchoconstriction is a recognised though rare problem.
Cost:
There are no data available directly assessing the cost effectiveness, although the cost is lower where good quality generic preparations are available. |
| REC 5 | Negative recommendation. At present, there is insufficient evidence to recommend intravenous magnesium as a routine second-line drug and is NOT recommended. However, if it is available, it may be worth trying if the patient continues to deteriorate despite other recommended treatment. |
| REC 6 | Negative recommendation. On the basis of the balance between benefits and risks, intravenous salbutamol is NOT recommended for use as a second-line drug. |
| REC 7 | Negative recommendation. On the basis of the balance between benefits and risks and because the risks outweigh the benefits in settings where monitoring of blood drug levels is not feasible, intravenous aminophylline is NOT recommended for routine use as a second-line drug. |
| Management of stable COPD |
|---|
| REC 1 | Benefits/risks:
When given as required beta agonists are effective in improving symptoms in patients with COPD. The effect of regular administration is unknown.
Values and acceptability:
Inhaled beta agonists are recommended rather than oral preparations because oral preparations have more pronounced undesirable effects that may be of particular relevance in view of common co-morbidities with COPD, e.g. arrhythmias in patients with coronary heart disease.
Cost:
There are no data available directly assessing the cost effectiveness, although the cost is lower where good quality generic preparations are available. It is feasible with an MDI. |
| REC 2 | Benefits/risks:
Theophylline can cause serious adverse effects, particularly if therapeutic blood concentrations are exceeded. Only low-dose slow-release theophylline can be recommended as being relatively safe and providing some efficacy.
Values and acceptability:
Low-dose, slow-release oral theophylline can be effective and well tolerated in the long-term treatment of stable COPD.
Cost:
No data available.
Feasibility:
As it is unlikely that blood levels can be monitored in resource-constrained settings, only low doses of theophylline are recommended. Patients should be advised to stop treatment and consult a doctor if adverse effects are experienced. |
| REC 3 | Negative recommendation. Oral corticosteroids (prednisolone) are ineffective in stable COPD except possibly in high doses when there are important side effects. On the basis of the balance between benefits and risks, oral steroids are NOT recommended for use in stable COPD. |
| REC 4 | Negative recommendation. When given in high doses, there may be a small benefit from inhaled steroids. However, high doses have more adverse effects and are more expensive, while any benefit is small. Their use for patients with stable COPD cannot be justified when resources are limited. |
| REC 5 | Negative recommendation. Compared to regular short-acting beta agonists, short-term inhaled ipratropium bromide has small benefits with regard to reducing symptoms and improving lung function. Currently, ipratropium bromide preparations are more expensive than beta agonists and there are no data to assess risk versus benefits of regular use over longer periods to recommend long-term regular use of ipratropium bromide, thus they are NOT recommended. |
| Management of exacerbation of COPD |
|---|
| REC 1 | Benefits/risks:
Since benefits significantly outweigh side effects, antibiotics should be given for all COPD exacerbations with purulent sputum and signs of systemic infection.
Values and acceptability:
Antibiotics are commonly prescribed empirically. Which antibiotic should be prescribed needs to be decided locally according to likely organisms, cost and availability.
Cost:
The cost depends on the antibiotic used. |
| REC 2 | Benefits/risks:
Benefits usually outweigh the risks. Short-term courses of oral steroids in the doses recommended are of benefit for acute exacerbations of COPD and usually have few side effects.
Values and acceptability:
A short course of oral steroids is beneficial and with the doses recommended is associated with minimum risk. However, it is important to weigh potential benefits against side effects for each patient.
Cost:
Affordable for resource-constrained settings.
Feasibility:
There should be easy access for patients with exacerbations of COPD. |
| REC 3 | Benefits/risks:
Effective for improving lung function in patients with acute exacerbations of COPD. For short-term administration for exacerbations, the benefits of high doses outweigh the risk of potential side effects. The evidence suggests no important advantages of nebulizers over spacers.
Cost:
There are no data available directly assessing the cost effectiveness, although the cost is lower where good quality generic preparations are available.
Feasibility:
Higher doses of inhaled beta agonists should be given to all patients with acute severe exacerbations of COPD where available. Administration either by MDI and spacer or by nebulization is acceptable. |
| REC 4 | Benefits/risks:
This recommendation is based on observational evidence and strong consensus belief that oxygen is beneficial. High concentrations of supplemental oxygen can lead to the accumulation of carbon dioxide and respiratory acidosis for some people with severe COPD. It is very important, therefore, that when oxygen is administered it is given in a low concentration (24%–28%) using a controlled oxygen delivery device. Patients clearly should not smoke if using or close to an oxygen supply.
Values and acceptability:
If oxygen is available, it should be administered for exacerbations of COPD, as long as a low concentration can be given as prescribed.
Cost:
Short-term use in exacerbations as recommended should be affordable. |
| REC 5 | Negative recommendation. Based on the available evidence, intravenous aminophylline is NOT recommended for routine use in acute exacerbations of COPD. Although there are data from only four studies, they show little evidence of benefit; thus any beneficial effect is likely to be small and the risks outweigh benefits. |