• Singapore Ministry of Health. Management of asthma. Singapore: Singapore Ministry of Health; 2008 Jan. 80 p. [99 references]

This is the current release of the guideline.

This guideline updates a previous version: Singapore Ministry of Health. Management of asthma. Singapore: Singapore Ministry of Health; 2002 Jan. 58 p.

Each recommendation is rated based on the level of the evidence and the grades of recommendation. Definitions of the level of evidence (1⁺⁺, 1⁺, 1^-, 2⁺⁺, 2⁺, 2^-, 3, 4) and the grades of recommendations (A, B, C, D and Good Practice Point [GPP]) are defined at the end of the "Major Recommendations" field.

The following is a list of major revisions or additions to the revised guidelines:

1. The key change is that asthma management is now focused on achieving control of asthma, rather than on an accurate classification of disease severity into mild, moderate or severe persistent asthma, which was in the previous clinical practice guideline (CPG).
2. A new classification based on control of asthma is now provided: Controlled, Partly Controlled, or Uncontrolled. This is a working scheme of management based on current opinion.
3. The use of a validated, simple and robust tool, the Asthma Control Test (ACT), is recommended for the assessment of control at each clinic visit.
4. Treatment is stepped up or down depending on the level of control achieved. A new treatment algorithm, based on the ACT score, is provided.
5. Clinical quality indices for asthma have been revised.

Objectives of Asthma Management

GPP - A successful management plan should be established for each patient in the context of a team effort that includes: the patient, relevant family member or carer, doctor, nurse/clinic assistant and pharmacist. It should involve the following elements:

• Education-motivation
• Self assessment and management
• Environmental management
• Pharmacological management

D - A new classification of asthma, guided by the level of asthma control, is recommended. (See table below). (Global Initiative for Asthma, 2006) Grade D, Level 4

Table: Levels of Asthma Control

* Lung function is not a reliable test for children 5 years and younger.

** Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate.

*** By definition, an exacerbation in any week makes that an uncontrolled asthma week.

A - All doctors treating asthma patients should provide patient education to aid behavior change. (Refer to Tables 1 and 2 in the original guideline document for details). (Gibson et al., 2001) Grade A, Level 1+

A - House dust mite is a universal allergen. No single measure is effective to reduce exposure to mite allergens. An integrated approach including barrier methods, dust removal, environmental mite control may be partially effective and should be used. (Morgan et al., 2004) Grade B, Level 2+

GPP - During periods of haze, patients should be advised to avoid strenuous exertion outdoors. GPP

C - The possibility of occupational asthma should be considered in a working adult with newly diagnosed asthma. The range of occupational sensitizers is large, and complex. If occupational asthma is suspected, the patient should be referred to a specialist for further assessment. (Nicholson et al., 2005) Grade C, Level 2+

B - Smoking should be avoided in all patients with asthma especially pregnant women and children. (Martinez et al., 1995; Dezateux et al., 1999) Grade B, Level 2+

A - Asthma medications can be given by various routes. The best route is by inhalation, because the drugs are given directly where they are needed, into the airways. This leads to faster action, with a much reduced risk of systemic side effects. (Brown PH et al.) Grade A, Level 1+

A - Inhaled corticosteroids are best used at low to moderate doses (refer to Table 4 in the original guideline document for details). (Powel & Gibson, "Inhaled corticosteroid," 2003; Szefler et al., 2002) Grade A, Level 1+

A - Long acting beta-2-agonists, including salmeterol and formoterol, should never be used as monotherapy in asthma. (Lemanski et al., 2001; Lazarus et al., 2001) Grade A, Level 1+

A - The strategy of "add on therapy" with long acting beta-2-agonists is recommended when a low to medium-dose of inhaled corticosteroids alone fails to achieve control of asthma. (O' Byrne et al., 2005; Scicchitano et al., 2004; Rabe et al., 2006; Vogelmeier et al., 2005) Grade A, Level 1++

A - Formoterol is a long acting beta-2-agonist, which has a rapid onset of action comparable to that of a rapid acting beta-2-agonist drug. If a combination inhaler containing formoterol and budesonide is considered, it may be used for both rescue and maintenance. This has been shown to reduce exacerbations and improve asthma control in adults and adolescents at relatively low doses of treatment. (O' Byrne et al., 2005; Scicchitano et al., 2004; Rabe et al., 2006; Vogelmeier et al., 2005) Grade A, Level 1++

B - Theophylline has a bronchodilator action and also modest anti-inflammatory properties. It cannot however be used as a controller drug. It may be useful as an add-on drug in patients who do not achieve good control on inhaled glucocorticosteroids alone. (Dahl, Larsen, & Venge, 2002; Evans et al., 1997) Grade B, Level 2++

A - Leukotriene modifiers such as montelukast have a small and variable bronchodilator effect, reducing symptoms including cough, improving lung function and reducing exacerbations and airway inflammation. It can either be used as an alternative to low dose inhaled glucocorticosteroids in patients with mild persistent asthma, or as an add-on drug when low dose inhaled glucocorticosteroids or when the combination of inhaled corticosteroids with long acting beta-2-agonist have not given the desired effect. (Laviolette et al., 1999; Lofdahl et al., 1999; Price et al., 2003; Vaquerizo et al., 2003) Grade A, Level 1+

A - The combination of inhaled ipratropium and inhaled beta-2-agonist may be used in the treatment of acute severe asthma exacerbation. Grade A, Level 1+

A - Short-term "burst" oral corticosteroids may be given at the dose of 40 to 50 mg/day for 5 to 10 days as treatment of severe acute exacerbation of asthma and in worsening asthma. Grade A, Level 1+

A - Regular low doses of oral steroids cause severe and intolerable long term side effects and should not be used in primary care. Grade A, Level 1+

A - The asthma clinical practice guidelines (CPG) workgroup recommends the Asthma Control Test (ACT), a 5-item, patient-administered survey questionnaire for assessing asthma control (Figure 1 in the original guideline document for details). This is a simple, objective, robust and validated method for monitoring control by doctors (and patients). (Global Initiative for Asthma, 2006; Nathan et al., 2004) Grade A, Level 1+

GPP - Patients who do not achieve good asthma control despite Step 4 levels of treatment have refractory asthma and should be reviewed by a specialist. Thus, management at Step 5 should be supervised directly by specialists. GPP

Management of Acute Exacerbations

GPP - Mild attacks (defined as reduction in peak flow of less than 20%, nocturnal awakening and increased use of short acting beta-2-agonist) can be treated at home. Beginning treatment at home also avoids treatment delays, prevents exacerbations from becoming severe, and also adds to patients' sense of control over their asthma. GPP

Treatment of Acute Asthma at the Clinic

GPP - Patients at high risk of dying from asthma require special attention, monitoring and care, particularly intensive education, including advice to seek medical care early during an exacerbation. GPP

Management of Adult Acute Asthma in the Clinic

Initial Treatment

B - Continuous inhaled, short-acting beta-2-agonist by nebulisation, one dose (e.g., salbutamol 5 to 10 mg) every 20 minutes for one hour; alternatively, the use of an inhaler (e.g., 20 puffs of salbutamol) plus a holding chamber (spacer device) produces equally effective bronchodilation. Grade B Level 2++

A - Addition of ipratropium 0.5 mg in adults to an aerosolised solution of beta-2-agonist has been shown to cause additional bronchodilation, particularly in those with severe airflow obstruction, and to reduce hospitalisation. Grade A Level 1++

A - Systemic corticosteroids e.g., prednisolone 30 mg, immediately and repeated for 7 to 10 days for all patients. No "tail" is needed and oral steroids are as rapid and effective as injections. Grade A Level 1+

At the Clinic Visit

GPP - The use of the Levels of Asthma Control table (see table above) and checklist is recommended on all patients at every visit.

Checklist:

1. Good Inhaler Technique
2. Compliance with preventive treatment
3. Compliance with follow-up visits
4. Reinforce Written Asthma Action Plan

GPP - Written Asthma Action Plan should be taught so that patients can implement it for self-management of exacerbations between visits (refer to section 5.3 and Annex A in the original guideline document for details) Patients should be advised to perform monthly self-audit of ACT scores between visits. GPP

GPP - Device proficiency should be emphasized at the first and every consultation. Education should include verbal instruction and demonstration of proper use of the devices by the health care providers. Patient should be encouraged to demonstrate their proficiency in the inhaler devices usage at every clinic visit. GPP

A - Asthma patients should be provided with a symptom-based written asthma action plan. Grade A, Level 1++

B - Doctors should ensure regular review of their patients who are unable to undertake guided self-management and adjust their medications according to their asthma control. (Powell & Gibson, "Options," 2003) Grade B, Level 2++

GPP - Patients should be provided with an appointment for review at regular intervals, depending on their asthma control status. During these follow-ups, the following measures may be included in the consultation:

1. Assess asthma control based on symptom frequency (referring to diary/calendar), impact on activities of daily living and/or PEFR measurements. Healthcare workers can assess asthma control using composite assessment tool, such as validated questionnaires like the Asthma Control Test (ACT). (Nathan et al., 2004)
2. Clarify and discuss patient's questions and asthma related problems, including the initial or previous treatment. (Patridge & Hill, 2000)
3. Check and correct inhaler device technique, if inappropriate.
4. Check patient's adherence/compliance to the medication plan.
5. Suggest measures to reduce exposure to trigger or risk factors.
6. Assess understanding of written asthma action plan and revise according to asthma control status. (Reddel, 2007) GPP

B - Asthmatic patients who are pregnant should be managed with inhalation therapy, which is safe and effective in pregnancy. Grade B, Level 2++

GPP - Primary care physicians can treat most asthma patients but may consider referring the following subsets of patients to respiratory physicians for further evaluation and/or management: those with other co-morbidity, confusing signs and symptoms and whose control is sub-optimal despite treatment with maximal drug dosages (3Cs).

1. Co-morbidity:
   1. Patient with concurrent heart failure, which may complicate asthma management.
   2. Patient with a history of psychiatric disease or multiple psychosocial problems, including the use of sedative.
   3. Patient with concurrent gastroesophageal reflux disease (GERD) which may mimic asthma.

2. Confusing sign and symptoms
   1. Patient with probable occupational asthma will require further diagnostic determination of the industrial trigger agent.
   2. Patient with atypical signs and symptoms such as unilateral wheezing to exclude other tracheobronchial pathology.

3. Control: Failure to achieve asthma control despite optimal treatment
   1. Patient who is currently using or have recently stopped using daily oral corticosteroid therapy.
   2. Patient with a history of near-fatal asthma requiring intubation and mechanical ventilation.
   3. Patient with severe asthma requiring step 4 care and yet experiencing exacerbation despite compliance to treatment.
   4. Patient with poorly controlled asthma (irregardless of asthma severity classification) who had at least two hospitalizations for asthma and/or requires more than two courses of burst therapies with oral corticosteroid in the past one year.

Management of Asthma in Children

B - A detailed medical history and clinical examination is mandatory. Additional tests like Pulmonary Function Tests (PFT), exhaled nitric oxide may be useful to support the diagnosis made or to monitor response to therapy for the more difficult patients. (Brindicci et al, 2007; Roberts et al., 2004) Grade B, Level 2+

A - Rapid-acting inhaled beta-2-agonists are the medications of choice for relief of bronchoconstriction and for the pre-treatment of exercise induced asthma. Beta-2-agonist metered-dose-inhaler (MDI) delivered by the holding chamber/spacer has been shown to be at least as effective as the nebuliser. Hence routine use of nebulisers is not recommended. During asthma exacerbations, as many as 4 to 8 puffs of salbutamol inhaler or 0.2 to 0.3 puffs/kg (max 10 puffs) may be used. (Cates et al. 2007; Schuh et al., 1999) Grade A, Level 1++

A - Long acting inhaled beta-2-agonists may be used as add-on therapy for children with symptoms which are not controlled with low dose inhaled steroids. These should not be used without concomitant inhaled corticosteroids. (Bisgaard et al., 2006) Grade A, Level 1+

A - Only formoterol may be used as a reliever medicine in view of its rapid onset of action. (O'Byrne, et al., 2005; Cabral et al., 2001; Hermansen et al., 2006) Grade A, Level 1+

A - Inhaled bronchodilators are preferred as they have quicker onset of action and fewer side effects than oral or IV administration. (Williams, Winner, & Clark, 1981) Grade A, Level 2+

B - For the younger children with nocturnal symptoms, oral long acting beta-2-agonists may be useful (Zarkovic et al., 2000). Sustained release theophylline can be useful for a short duration. It is important to monitor for side effects such as agitation, muscle tremors, palpitations and headache. (Ellis, 1985; Bender et al., 1991; Rachelefszky et al., 1986; Schlieper et al., 1991) Grade B, Level 2+

A - In older children above 5 years, leukotriene modifiers may be used as they provide clinical benefit at all levels of asthma severity. However, clinical benefits are generally less than those with inhaled corticosteroids. (Garcia et al., 2005; Ng, Salvio, & Hicks 2004; Ducharme & Di Salvio, 2007) Grade A, Level 1++

A - Leukotriene modifiers may be used to reduce viral induced asthma exacerbation in younger children aged 2 to 5 years. (Bisgaard, et al., 2005) Grade A, Level 1+

A - Leukotriene modifiers may be used as an add-on therapy in children on low to moderate doses of inhaled steroids. In children with poor asthma control, adding a leukotriene modifier may provide additional benefit, including reducing the number of exacerbations. (Phipatanakul et al., 2003) Grade A, Level 1+

A - A long acting beta-agonist or a leukotriene modifier should be added rather than increasing the dose of inhaled steroids if children with mild persistent asthma do not show clinical improvement with inhaled steroids alone. (Nelson et al., 2000; Fish et al., 2001; Bestall & Jones, 2007) Grade A, Level 1+

A - Combination agents containing long acting inhaled beta-2-agonists and inhaled steroids may be used in children above 5 years of age whose control is not optimum with low dose inhaled steroids. (Bisgaard et al., 2006; Noonan et al., 2006) Grade A, Level 1+

GPP - Recommended in choosing an inhaler device for children:

<4 years: MDI with spacer + a facemask

4-6 years: MDI with spacer with mouthpiece

>6 years: MDI with spacer with mouthpiece or dry powder inhaler, e.g., accuhaler and turbuhaler

GPP - Follow-up assessment is best achieved with a review of peak expiratory flow rate (PEFR) and symptom control. It is important to check for compliance, inhaler technique and correct use of a spacer device at each visit. The treatment should be kept as simple as possible, preferably once or twice a day dosing. For older children, new inhaler devices, e.g., turbuhalers, and other breath-activated devices may enhanced drug delivery and encourage compliance. GPP

GPP - Anti-inflammatory therapy ought to be maintained for at least 3 months after adequate control of symptoms. The child should be reviewed regularly thereafter with the view to reducing therapy to the minimum amount to maintain control of asthma. Should symptoms relapse during the tapering of maintenance doses, step-up of dosage may be necessary to achieve good control (after ensuring good compliance and inhaler technique). GPP

A - The initiation of long-term control therapy is recommended for reducing impairment and risk of exacerbations in infants and young children who had four or more episodes of wheezing in the past year that lasted more than 1 day and affected sleep AND who have either:

1. One of the following: a parental history of asthma, a physician's diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens

   OR

2. Two of the following: evidence of Immunoglobulin E (IgE) sensitization to foods, ≥4 percent peripheral blood eosinophilia, or wheezing apart from colds. (Castro-Rodriguez et al., 2000) Grade A, Level 1+

A - Inhaled corticosteroids should be used to control symptoms, prevent exacerbations, and improve the child's quality of life, but their use should not be initiated or prolonged for the purpose of changing the progression or underlying severity of the disease. Grade A, Level 1+

GPP - The asthmatic child should be referred to a specialist for evaluation and management advice when he or she:

1. Has high risk asthma with poor asthma control

   OR

2. Is below 3 years and requires moderate to high doses of inhaled steroids and not responding as expected

   OR

3. Requires high dose steroids, BDP/BUD >400 mcg/day or fluticasone >200 mcg/day, or is on prolonged inhaled steroid therapy for more than 6 months and remains symptomatic. GPP

GPP - When an acute exacerbation is expected, e.g. during an acute upper respiratory infection, the usual medications should be stepped up:

1. Frequent beta-2-agonist (e.g., salbutamol MDI 0.2 to 0.3 puffs/kg), should be given at 4 hourly intervals, preferably via a spacer device.
2. For selected patients who have severe asthma or with a past history of acute sudden severe attacks, the action plan should include the need to increase the dose of inhaled steroids and rarely to start a course of oral prednisolone.

A - It is strongly recommended that clear written asthma action plans be given to the family on how to manage acute exacerbations based on symptoms. (Toelle & Ram, 2007) Grade A, Level 1+

GPP - It is recommended that symptom assessment and objective measurement of severity with PEFR be used in assessment of acute asthma whenever possible. GPP

A - An inhaled bronchodilator should be given at 15 to 20 minute intervals and the child reviewed thereafter. Grade A, Level 1+

GPP - Admission for a child should be considered with any of the following:

1. Shows no or poor response to a beta-2-agonist
2. Requires an inhaled beta-2-agonist more frequently than 4 hourly
3. Has acute asthma and has a past history of acute life threatening asthma GPP

GPP - A short course of steroids should be considered when the child meets one of the following criteria:

1. Requires frequent beta-2-agonist therapy (more frequent than 3 hourly)
2. Requires regular nebuliser therapy (3 to 4 hourly) for more than 36 to 48 hours
3. Has a past history of a severe life threatening episode
4. Is on high dose inhaled steroids or low dose oral steroids GPP

D & GPP - A dose of prednisolone of 1 to 2 mg/kg per day (max 40 mg) is usually given for no longer than 5 days. (Global Initiative for Asthma, 2006; Bacharier et al., 2008) A child who has suffered from a severe acute attack and requires prolonged or repeated oral steroids for control should be referred to a specialist for assessment of treatment. Grade D, Level 4, GPP

Definitions:

Levels of Evidence

Level 1⁺⁺

High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias.

Level 1⁺

Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.

Level 1^-

Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias.

Level 2⁺⁺

High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal.

Level 2⁺

Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal.

Level 2^-

Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal.

Level 3

Non-analytic studies, e.g., case reports, case series.

Level 4

Expert opinion

Grades of Recommendation

Grade A: At least one meta-analysis, systematic review of RCTs, or RCT rated as 1^{+ +} and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1⁺, directly applicable to the target population, and demonstrating overall consistency of results.

Grade B: A body of evidence including studies rated as 2⁺⁺, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1^{+ +} or 1⁺

Grade C: A body of evidence including studies rated as 2⁺, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2^{+ +}

Grade D: Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2⁺

GPP (Good Practice Points): Recommended best practice based on the clinical experience of the guideline development group.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

• Singapore Ministry of Health. Management of asthma. Singapore: Singapore Ministry of Health; 2008 Jan. 80 p. [99 references]

Not applicable: The guideline was not adapted from another source.

2002 Jan (revised 2008 Jan)

National Medical Research Council (Singapore Ministry of Health) - National Government Agency [Non-U.S.]
Singapore Ministry of Health - National Government Agency [Non-U.S.]

Singapore Ministry of Health

Workgroup on Management of Asthma

Workgroup Members: Dr John Abisheganaden (Chairperson) Senior Consultant, Dept of Respiratory Medicine, Tan Tock Seng Hospital; Dr Hui Kok Pheng, Hui Kok Pheng Respiratory and Internal Medicine Clinic, Mt Elizabeth Medical Centre; A/Prof Daniel Goh Yam Thiam, Chief & Senior Consultant, Dept of Paediatrics, National University Hospital; A/Prof Chay Oh Moh, Chairman, Division of Paediatrics, Dept of Paediatric Medicine, KK Women and Children's Hospital; A/Prof Lee Bee Wah, Adjunct Associate Professor, Dept of Paediatrics, National University Hospital; Dr Tan Ngiap Chuan, Director, SingHealth Polyclinics-Pasir Ris; A/Prof Sin Fai Lam, Head, Dept of Medicine, Alexandra Hospital; Dr K Narendran, Deputy Chief & Senior Consultant, Dept of General Medicine, Changi General Hospital; Dr Tan Keng Leong, Senior Consultant, Dept of Respiratory and Critical Care Medicine, Singapore General Hospital; Dr Chong Phui Nah, Deputy Director, Medical Manpower Development, Clinical Services, NHG Polyclinics HQ; Prof. Lim Tow Keang, Head, Division of Respiratory & Critical Care Medicine, Dept of Medicine, National University Hospital; Dr Gong Swee Choo, King George's Medical Centre; N/O Lathy Prabhakaran, Dept of Nursing Services, Tan Tock Seng Hospital

Not stated

This is the current release of the guideline.

This guideline updates a previous version: Singapore Ministry of Health. Management of asthma. Singapore: Singapore Ministry of Health; 2002 Jan. 58 p.

None available

This NGC summary was completed by ECRI on December 19, 2002. The information was verified by the guideline developer on January 29, 2003. This summary was updated by ECRI on December 5, 2005 following the U.S. Food and Drug Administration (FDA) advisory on long-acting beta2-adrenergic agonists (LABA). This summary was updated by ECRI Institute on May 30, 2008.