CLINICAL PRACTICE GUIDELINES FOR MANAGEMENT OF ADULT ASTHMA

A JOINT STATEMENT OF THE

MALAYSIAN THORACIC SOCIETY

MINISTRY OF HEALTH MALAYSIA

ACADEMY OF MEDICINE OF MALAYSIA

REVISED 2002

COMMITTEE MEMBERS:
Zainudin Md. Zin, FRCP (Chairman) Damansara Specialist Hospital, Selangor Aziah Ahmad Mahayiddin, FCCP Hospital Kuala Lumpur Abdul Wahab Sufarlan, FRCP Ampang Puteri Specialist Hospital, Selangor Hooi Lai Ngoh, FRCP Hospital Pulau Pinang, Pulau Pinang George Kutty Simon, FRCP Hospital Alor Setar, Kedah Kuppusamy Iyawoo, FRCP Institute of Respiratory Medicine, Kuala Lumpur Kwa Siew Kim, FRACGP Academy of Family Physicians, Malaysia Leong Kwok Chi, FRACGP Academy of Family Physicians, Malaysia Liam Chong Kin, FRCP University Malaya Medical Centre, Kuala Lumpur Roslan Harun, PhD Hospital Universiti Kebangsaan Malaysia, Kuala Lumpur Wong Wing Keen, MRCP Sunway Medical Centre, Selangor

Foreword

Asthma is a major global health problem. Its prevalence is increasing everywhere both in children and adults. The World Health Organization (WHO) estimated in 1998 that asthma affected 155 million people worldwide. In Malaysia, it is estimated about 1.5-1.8 million people are affected by the disease. The burden of asthma on economy is considerable both in terms of direct medical costs such as hospitalization and pharmaceuticals and indirect medical costs such as time lost from work and premature deaths. Asthma morbidity too is considerable with many patients have symptoms that affect their quality of life such as sleep, exercise and social activities. Asthma accounted for 0.4% of all deaths, or 1 in 250 and many of these deaths were thought to be preventable if asthma was managed properly or patients acted appropriately. The morbidity and economic burden of asthma can be substantially reduced if asthma is under control and one way to achieve that is to equip doctors with the necessary knowledge on asthma management. Guidelines for management of adult asthma was first published by the Malaysian Thoracic Society in 1996 with the aim of providing up-to-date information on asthma management for doctors at all level of care. Several years have gone and many new findings and scientific information are now available which necessitates the revision of the guidelines. It is a privilege for me to be able to work with a group of highly dedicated and motivated people to revise these guidelines. I wish to acknowledge the good work of the committee members who had contributed towards the success of the revision and the contribution of others through their comments. The revision of the guidelines and the activities for the dissemination of the document were conducted through educational grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Merck Sharp & Dohme. I wish to express my gratitude and thanks to these companies for their generous support. The committee members are however, solely responsible for the statements and conclusions presented in this document. These guidelines are meant to serve as guides and doctors are expected to use their best judgement and act accordingly when treating their patients based on patients clinical conditions, the availability of facilities and resources.

Zainudin Bin Md Zin, MD,FRCP,FCCP,FAMM Chairman of the Committee Guidelines for Management of Adult Asthma (Revision 2002)

Contents

Foreword
Introduction
1. 2. 3. 4. 5. EPIDEMIOLOGY DEFINITION PATHOGENESIS DIAGNOSING ASTHMA MANAGEMENT OF CHRONIC ASTHMA 5.1 The aims of management 5.2 Approach to management 5.3 Drug treatment 5.3a Anti-inflammatory medications (i) Corticosteroids (ii) Cromones (iii) Antileukotrienes Long acting bronchodilators (i) Long acting beta2-agonists (ii) Sustained-release theophyllines Short acting bronchodilators (i) Beta2-agonists (ii) Anticholinergic drugs (iii) Methylxanthines (iv) Other treatment Drug delivery i 1 1 1 2 3 3 3 3 3 3 3 4 4 4 4 4 5 5 5 9 9 10 11 11 12

5.3b

5.3c

5.4 6. 7. 8.

EDUCATION OF PATIENT AND FAMILY AVOIDANCE OF PRECIPITATING FACTORS ASSESSMENT OF SEVERITY AND RESPONSE TO TREATMENT 8.1 Clinical assessment 8.1a Measuring peak expiratory flow (PEF)

9. 10. 11. 12

APPROACH TO DRUG THERAPY - STEPWISE APPROACH RESCUE COURSE OF STEROID TABLETS FOLLOW-UP AND MONITORING MANAGEMENT OF ASTHMA IN PREGNANCY 12.1 Introduction 12.2 Management 12.3 Labour 12.4 Breastfeeding GUIDELINES FOR THE MANAGEMENT OF ACUTE ASTHMA IN ADULTS 13.1 Aims of management 13.2 Assessment 13.3 Features of mild asthma attack 13.4 Features of moderately severe asthma attack 13.5 Features of very severe asthma attack 13.6 Features of life-threatening asthma MANAGEMENT OF ACUTE ASTHMA IN AN OUTPATIENT SETTING (i) INITIAL PEF >75% (Mild acute asthma) (ii) INITIAL PEF < 75% (this includes moderately severe to lifethreatening asthma) SUBSEQUENT MANAGEMENT IN THE WARD 15.1 Monitoring the response to treatment 15.2 Other investigations MANAGEMENT IN INTENSIVE CARE UNIT DISCHARGE PLAN FOR HOSPITALISED PATIENT MANAGEMENT OF ACUTE ASTHMA IN GENERAL PRACTICE

12 14 14 15 15 15 16 16 17 17 17 17 18 18 18 19 19 19 22 22 22 23 23 23 25 27 28

13.

14.

15.

16. 17. 18.

Appendix 1 Example of a written asthma management plan Appendix 2 PEF normogram References

Introduction
Asthma is a common disease causing significant morbidity and mortality worldwide. With appropriate treatment and care most of this morbidity can be avoided and many deaths attributable to asthma can be prevented. Since the last decade, clinical practice guidelines have become an important tool to improve knowledge in the management of various common diseases including asthma. In 1995, the Malaysian Thoracic Society set up an expert committee to work on the guidelines for the management of asthma in adults with the aim of providing up-to-date information on asthma management to health care providers taking into account local practices and the availability of resources. The guidelines were completed and published in 1996 and circulated to doctors working in the government and private sector. Since then many new findings and advances have been made in asthma management which necessitated the revision of the guidelines. In one of its council meetings, the Malaysian Thoracic Society decided to invite all the previous expert committee members to once again sit in the new committee to revise the guidelines. In addition, a few new members including two representatives from the Academy of Family Physicians of Malaysia were invited to ensure views of family physicians were given due consideration. The committee held four meetings, each for duration of one and a half days on 4 weekends from early 2000. The committee was divided into 4 groups and each group was responsible to revise its assigned section. Group 1 covered epidemiology, definition, pathogenesis and diagnosis; group 2 covered non-pharmacological management, assessment of severity and asthma in pregnancy; group 3 covered pharmacotherapy and drug treatment of chronic asthma; and group 4 covered management of acute asthma. Unlike the first guidelines, in which treatment recommendations were mainly by consensus, the present guidelines emphasised recommendations based on scientific evidence as far as possible. Members had agreed to assign levels of evidence to statements based on the system developed by the National Heart, Lung and Blood Institute, Maryland, USA (Table A). The draft of the guidelines was circulated to members of the Malaysian Thoracic Society and selected physicians for their comments. The guidelines were also discussed at a Clinical Practice Guidelines Workshop jointly organised by the Ministry of Health and the Academy of Medicine of Malaysia on October 12, 2002. The revised draft was circulated again to the expert committee after all the comments from the reviewers were deliberated before the document was sent to Health Technology Assessment Unit, Medical Development Division, Ministry of Health for approval for adoption as national policy prior to publication and distribution. The committee realised that an effective mechanism for dissemination of the guidelines is important to ensure that the guidelines reach as many practitioners as possible and a follow up study is needed to determine its effectiveness. i

Table A: Description of Level of Evidence Evidence Category

A

Sources of Evidence
Randomised controlled trials (RCTs). Rich body of data.

Definition
Evidence is from endpoints of well designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made. Category A requires substantial numbers of studies involving substantial numbers of participants.

Randomised controlled trials (RCTs). Limited body of data.

Evidence is from endpoints of intervention studies that include only limited number patients, post hoc or subgroup analysis of RCTs, or metaanalysis of RCTs. In general, category B pertains when few randomised trials exist, they are small in size, they were undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent. Evidence is from outcomes of uncontrolled or nonrandomised trials or from observational studies. This category is used only in cases where the provision of some guidance was deemed valuable but the clinical literature addressing the subject was insufficient to justify placement in one of the other categories. The panel consensus is based on clinical experience or knowledge that does not meet the above-listed criteria.

Nonrandomised trials. Observational studies.

Panel consensus judgement.

ii

1.

EPIDEMIOLOGY

Asthma is a common disease with unacceptably high morbidity and mortality. Asthma prevalence is increasing worldwide and it is commonly under diagnosed and undertreated. In a large survey of asthmatics in 8 areas in the Asia Pacific region, only 13.6% of respondents were on inhaled corticosteroids despite almost half of them having symptoms of persistent asthma1. Many asthma deaths and morbidity have been associated with inadequate treatment, under-use of objective measurement of severity and inadequate supervision2-4. In Malaysia, the prevalence of asthma in primary school children is reported as 13.8%5 and in children aged 13-14 years is 9.6%6 . The prevalence of self-reported asthma in adults as reported in a Ministry of Health Second National Health and Morbidity Survey is 4.1%7. In the same study, the Chinese recorded significantly lower prevalence of asthma (2.4%) than other races (5.6%). This survey and other studies also confirmed underdiagnosis of the disease, inappropriate treatment and under-use of peak flow measurements8,9. Only 36.1% of adult asthmatics ever had their peak flow measured. The survey also reported that the prevalence of asthma was higher in rural (4.5%) than in urban areas (4.0%)7. There was a higher prevalence of asthma in those with lower educational status (5.6%) and lower income (4.7%). The majority of patients (87.3%) had mild asthma; 9.9% had moderate asthma and 2.7% had severe asthma. Among the severe asthmatics, only 19.4% were on inhaled corticosteroids. The duration of days ill due to asthma was 4.2 days per episode while days off work or school were 2.4 days per episode, indicating significant morbidity and socio-economic impact of the disease.

2.

DEFINITION

Asthma, irrespective of severity, is a chronic inflammatory disorder of the airways10. This has implication in the diagnosis, management and prevention of the disease. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and cough particularly at night and in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment.

3.

PATHOGENESIS

The inflammatory features of asthma include: mucosal oedema and increased vascular permeability denudation of airway epithelium collagen deposition beneath the basement membrane hypertrophy and hyperplasia of bronchial smooth muscles and mucus glands 1

 inflammatory cell infiltration and activation of - neutrophils - eosinophils - mast cells - T and B lymphocytes cytokine production Airway inflammation contributes to bronchial hyper-responsiveness, airflow limitation, respiratory symptoms and disease chronicity. Acute inflammation causes airway obstruction as a result of smooth muscle bronchospasm, mucosal oedema and mucus plug formation. Persistent chronic airway inflammation may result in airway remodeling which leads to irreversible bronchial obstruction. Atopy, the genetic predisposition for the development of an IgE-mediated response to common allergens, is the strongest identifiable predisposing factor for developing asthma.

4.

DIAGNOSING ASTHMA

Consider asthma if any of the following signs or symptoms are present:

Wheezing

high-pitched whistling sounds when breathing out (A normal chest

examination does not exclude asthma). History of any of the following: cough, worse particularly at night/early morning recurrent difficulty in breathing recurrent wheeze recurrent chest tightness

Note: Eczema, hay fever, or a family history of asthma or atopic diseases is often associated with asthma.

Symptoms occur or worsen at night/early morning, awakening the patient Symptoms occur or worsen in the presence of: exercise animals pollen aerosol chemicals dust mites (in mattress, pillows, upholstered furniture, carpets) respiratory tract infection smoke (tobacco, wood) changes in temperature drugs (aspirin, beta blockers) strong emotional expression (laughing or crying hard)

Reversible and variable airflow limitation-as measured by a peak expiratory flow (PEF) meter in any of the following ways: PEF increases more than 15% 15 to 20 minutes after inhaling a short-acting beta2-agonist, or PEF varies more than 20% from morning measurement upon arising to measurement 12 hours later in patients who are taking a bronchodilator (more than 10% in patients who are not taking a bronchodilator), or PEF decreases more than 15% after 6 minutes of running or exercise

5.
5.1

MANAGEMENT OF CHRONIC ASTHMA

The aims of management are To abolish day and night symptoms of asthma To restore normal or best possible long term airway function To prevent most acute attacks To prevent mortality Approach to management In order to achieve those aims the approach to management should include:-

5.2

Educating patient and family members Identifying and avoiding trigger factors Assessing severity and monitoring response to treatment Selecting appropriate medications and using the lowest effective dose to minimise short and long term side effects Drug treatment There are 3 major groups of medications to treat asthma (refer to table 1)

5.3

a) b) c) 5.3a)

Anti-inflammatory medications Long-acting bronchodilators Short-acting bronchodilators Anti-inflammatory medications As asthma is a chronic inflammatory condition, anti-inflammatory drugs should be a logical treatment for most patients except for those with intermittent asthma. Reducing the inflammation will decrease bronchial hyper-responsiveness. The types of anti-inflammatory medications include: (i) Corticosteroids Corticosteroids are the main prophylactic drugs in adult asthmatics11-15 (Evidence A). They should be taken by inhalation and the dosage should be kept to a minimum to reduce side effects (usually local side effects)16. Long-term oral steroids may be required for severe persistent asthma. (ii) Cromones This group of medications is safe with no significant side effects. It is given by inhalation (powder Spinhaler or metered dose inhaler). It is effective in the symptomatic and prophylactic management of mild persistent asthma but less effective than inhaled corticosteroids in more severe asthma17-20(Evidence A). 3

(iii) Antileukotrienes This new group of anti-inflammatory medication has been shown to have some effect in controlling mild persistent asthma21(Evidence A). Compared to low dose inhaled corticosteroids they have similar efficacy in reducing the rate of asthma exacerbations but low dose inhaled corticosteroids appear to be more effective in improving lung function, quality of life, reducing symptoms and the need for rescue beta2-agonists22(Evidence A). They have also been shown to reduce the requirement for high doses of inhaled corticosteroids23(Evidence B). They may also be used for aspirin sensitive asthma24(Evidence A) and exerciseinduced asthma25(Evidence B). 5.3b) Long-acting bronchodilators These medications should be used concomitantly with anti-inflammatory medications for long-term control of symptoms. This group consists of longacting beta2-agonists and sustained-release theophyllines. (i) Long-acting beta2-agonists Long-acting beta2-agonists should be used in combination with inhaled corticosteroids. The combination of long-acting beta2-agonists with inhaled corticosteroids usually gives more effective control than increasing the dose of inhaled corticosteroids alone26-31(Evidence A). These medications, except formoterol, are not recommended for treatment of acute symptoms or exacerbations32. Fixed dose combination inhaler of corticosteroid with long-acting beta2-agonists (e.g. fluticasone/salmeterol, budesonide/formoterol) improves patient compliance and hence control. (ii) Sustained-release theophyllines This group of drugs may be used with inhaled corticosteroids for persistent asthma when long-acting beta2-agonists are not available. Their usefulness is limited by variable metabolism and a narrow therapeutic window. Sustained release preparations may be used in nocturnal asthma33,34(Evidence B). 5.3c) Short-acting bronchodilators These medications are used to relieve symptoms of acute asthma. They should be used as required rather than regularly. This group consists of beta2-agonists, anticholinergic drugs and methylxanthines.

(i) Beta2-agonists These drugs are the most effective bronchodilators available. They are safe with few side effects when taken by inhalation. The therapeutic effect is felt within a few minutes of inhalation. (ii) Anticholinergic drugs Inhaled anticholinergics have slower onset but longer duration of action than short-acting beta2-agonists. In asthma, they are generally weaker bronchodilators than beta2-agonists. They have few side effects. (iii) Methylxanthines These drugs are available in oral and parenteral forms. Parenteral forms are used in the management of acute severe asthma. Oral short-acting theophyllines have limited role in the management of asthma. NB: Inhaled beta2-agonists are the bronchodilator of choice. As far as possible avoid using anti-cholinergics or xanthines as first line bronchodilator drugs. (iv) Other treatment Anti-histamines including ketotifen have been shown to be of limited efficacy in many clinical trials in asthma35-37. The role of hyposensitisation or allergenspecific immunotherapy has been studied but the results are conflicting38-40. At the moment it cannot be recommended as standard treatment.

Table 1. Types Of Asthma Medications

Table 1a ANTI-INFLAMMATORY MEDICATIONS

Drug class

Generic names Beclomethasone Budesonide Fluticasone

Side effects Inhaled: Oral candidiasis and dysphonia. More than 1 mg a day may be associated with skin thinning, easy bruising, adrenal suppression and cataracts (Evidence C). Inhaled:

Remarks Potential but small risk of side effects is outweighed by efficacy. Spacer devices and mouth washing after inhalation decreases oral candidiasis.

(i) Corticosteroids Inhaled:

Oral: Prednisolone Dexamethasone

Oral: Long-term use may lead to osteoporosis, hypertension, diabetes, cataracts, adrenal suppression, obesity,

Oral: If used long term, alternate day morning dosing produces less toxicity. For short-term use, a 3 to 10 day course is effective for

skin thinning and myopathy. gaining control. Parenteral: Hydrocortisone Methylprednisolone Parenteral: To be used only in the treatment of acute severe asthma.

(ii) Cromones

Sodium cromoglycate

None or minimal

May take 4-6 weeks to achieve maximum effect.

(iii) Antileukotrienes

Montelukast

Possible elevation of liver enzymes and bilirubin

Possible role as an alternative to low dose inhaled corticosteroids an as add-on therapy to inhaled corticosteroids.

Table 1b LONG-ACTING BRONCHODILATORS

Drug class

Generic names Inhaled: Formoterol Salmeterol

Side effects Inhaled: Beta2-agonists have fewer side effects than oral formulations. Inhaled:

Remarks These formulations are not to be used to treat acute attacks with the exception of formoterol.

(i) Long-acting beta2-agonists

Oral: Bambuterol Salbutamol SR Terbutaline SR Clenbuterol

Oral: Oral beta2-agonists may cause tachycardia, palpitations, tremors, anxiety, headache and hypokalaemia.

Should always be used in combination with inhaled corticosteroids.

(ii) Long-acting methylxanthines

Sustained-release theophylline

Nausea, vomiting, headache, tremor and insomnia. Serious side effects such as seizures and arrhythmias can occur especially at higher serum concentrations.

Serum theophylline levels should be monitored when high doses are used and in special circumstances, eg. liver failure and cardiac failure. Interactions with other drugs such as cimetidine,macrolides and rifampicin can occur.

Table 1c SHORT-ACTING BRONCHODILATORS

Drug class

Generic names Salbutamol Terbutaline Fenoterol

Side effects Beta2-agonists may cause tachycardia, tremor and irritability. Inhaled beta2agonists have fewer side effects than oral and parenteral preparations.

Remarks Drugs of choice for relief of acute bronchospasm. Inhaled route has faster onset and is more effective than oral route. Parenteral salbutamol or terbutaline may be used in acute severe attacks.

(i) Short-acting beta2-agonists

(ii) Anticholinergics

Ipratropium bromide

Minimal mouth dryness.

May provide additive effect to beta2-agonists. Onset of action is slower.

(iii) Short-acting methylxanthines

Short acting theophylline

Nausea, vomiting, headache, tremor and insomnia. Serious side effects such as seizures and arrhythmias can occur especially at higher serum concentrations.

May be used if beta2-agonists are not available.

(iv) Nonselective adrenergic agonists

Adrenaline/ epinephrine injection

Similar but more significant side effects than beta2-agonists.

Not recommended for treating asthma attacks if beta2agonists are available.

5.4

Drug delivery

The inhaled route is preferred for beta2-agonists and steroids as it produces the same benefit with fewer side effects as compared to the oral route. In addition, inhaled medications exert their effects at lower doses41,42. The pressurised metered dose inhaler (MDI) is suitable for most patients as long as the inhalation technique is correct. For patients with poor coordination, alternative methods for drug inhalation include spacer devices, dry powder inhalers and breath-actuated pressurised MDI42-47. The nebulised route is preferred in the management of acute attacks.

6.

EDUCATION OF PATIENT AND FAMILY

This is an important but often neglected aspect in the management of asthma. It is essential in ensuring the patients cooperation and compliance with therapy. As far as possible patients and their families should be encouraged and trained to actively participate in the management of their own asthma. Patient education should include the following information: i. ii. Nature of asthma Preventive measures/avoidance of triggers

iii. Drugs used and their side-effects iv. Proper technique of using inhaled drugs v. Peak flow monitoring vi. Recognition of features of worsening asthma (increase in brochodilator requirement, vii. Knowledge of the difference between relieving and preventive medications development of nocturnal symptoms, deteriorating peak flow rates) viii. Self management plan (appendix 1) ix. The danger of non-prescribed self medication including certain traditional medicines

7.

AVOIDANCE OF PRECIPITATING FACTORS

Exposure of asthmatic patients to irritants and allergens to which they are sensitive has been shown to increase asthma symptoms and precipitate asthma episodes.

Table 2. Common Asthma Triggers Trigger factors

1 2
Beta blockers Tobacco smoke (active or passive smoking) Air pollution House dust mites

Recommendations
Avoid using beta-blockers (Evidence C) Stay away from tobacco smoke. Patients should not smoke

3 4

Physical exertion should be avoided when levels of air pollution are high (Evidence C) Avoid whenever possible but current chemical and physical methods aimed at reducing exposure seem to be ineffective and cannot be recommended as prophylaxis for mite sensitive asthmatics48 (Evidence A) Remove animals from the home, or at least from the sleeping area (Evidence C) Do not avoid physical activity. Symptoms can be prevented by taking short or long-acting inhaled beta2-agonist at appropriate time before strenuous exercise Adult patients with severe persistent asthma, nasal polyps or a history of sensitivity to aspirin or nonsteroidal anti-inflammatory drugs should be counseled regarding the risk of severe and even fatal exacerbations from using these drugs (Evidence C) Should be avoided whenever possible (Evidence C)

5 6

Allergens from animals with fur Physical activity

Aspirin and nonsteroidal anti-inflammatory drugs Other identified allergens e.g. food, pollen, cockroach allergen Occupational exposure Rhinitis, sinusitis and gastroesophageal reflux

9 10

Change of occupation may be necessary (Evidence C) These conditions should be treated (Evidence C)

10

8.

ASSESSMENT OF SEVERITY AND RESPONSE TO TREATMENT

Assessment should be done as follows:

8.1

Clinical assessment This should include patients symptoms, sleep disturbances, disturbance of daily activities and the frequency of bronchodilator drug and/or rescue courses of steroid used.

Table 3. Classification of Asthma Severity

CLASSIFICATION OF ASTHMA SEVERITY BEFORE TREATMENT

Symptoms Severe Persistent Moderate Persistent Night time Symptoms PEF

Daily Frequent exacerbations Limitation of physical activity Daily Daily use of beta2-agonist Exacerbations affect activity and sleep > 1 time a week but < 1 time a day Exacerbations may affect activity and sleep < 1 time a week Brief exacerbations Asymptomatic and normal PEF between exacerbations

Frequent

< 60% predicted Variability > 30%

> 1 time a week

> 60% - < 80% predicted Variability > 30%

Mild Persistent

> 2 times a month

> 80% predicted Variability 20-30%

Intermittent

< 2 times a month

> 80% predicted Variability < 20%

11

a. Measuring peak expiratory flow (PEF) This can be measured by a peak flow meter.

PEF Measurements
(i) During periods of well-being This allows measurement of the patients best PEF value which will provide the target for the doctor and the patient to aim for. Twice daily measurements (morning and evening) before any inhaled bronchodilator treatment will determine the diurnal variability of airway calibre. This is calculated as the range divided by the highest value and expressed as a percentage. PEF (max) PEF (min) PEF (max) Good control of asthma means PEF variability is maintained at less than 10%. (ii) During symptomatic episodes During an attack of asthma PEF fairly accurately measures the degree of bronchospasm. A PEF of less than 50% of normal or best suggests a very severe attack and a PEF of less than 30% suggests a life-threatening attack. When the best PEF value is not known, a single reading of less than 200 L/min usually indicates a severe attack. In addition to history and physical findings the PEF helps the doctor decides on the appropriate therapy. As far as possible patients with moderate and severe persistent asthma should regularly measure their PEF twice a day. Comparison to local normal values should be made49 (appendix 2). The classification of asthma severity based on symptoms, bronchodilator usage and PEF reading is summarised in Table 3. x 100 = _______ %

9.

APPROACH TO DRUG THERAPY - STEPWISE APPROACH

Treatment should be carried out in a stepwise manner. Patients should be started on treatment at the step most appropriate for the initial severity of their condition (Table 4). Treatment would then be changed (stepped-up or stepped-down) according to their progress.

12

Table 4. Treatment of Adult Asthma TREATMENT OF ADULT ASTHMA

Preferred treatments are in bold print Patient education is essential at every step
Long-Term Preventive Quick-Relief

Daily medications: Inhaled corticosteroid*, 800-2000 mcg, and

Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms

STEP 4
Severe Persistent

Long-acting bronchodilator: either inhaled long-acting beta2-agonist and/or sustainedrelease theophylline, and/or oral long acting beta2-agonist, and Oral corticosteroid long term Daily medications: Inhaled corticosteroid*,500-1000 mcg AND, if needed Long-acting bronchodilator: either inhaled long-acting beta2-agonist, sustained-release

Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms

STEP 3
Moderate Persistent

theophylline, or oral long acting beta2-agonist (Inhaled long-acting beta2-agonist may provide more effective symptom control when added to low-medium dose steroid compared to increasing the steroid dose) Consider adding anti-leukotriene, especially for aspirin-sensitive patients and for preventing exercise-induced bronchospasm Daily medications: Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms

STEP 2
Mild Persistent

Either Inhaled corticosteroid*, 200-500 mcg, or cromoglycate or sustained-release theophylline or anti-leukotrienes

None needed

Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms, but less than once a week Inhaled beta2-agonist or cromoglycate before exercise or exposure to allergen
13

STEP 1
Intermittent

*Inhaled corticosteroid: Beclomethasone dipropionate (BDP) or budesonide. For fluticasone the equivalent dose is half of BDP/budesonide.

Step down
Patients should be reviewed regularly. When the patients condition has been stable for 3-6 months, drug therapy may be stepped down gradually. The monitoring of symptoms and peak flow rate should be continued during drug reduction.

10.

RESCUE COURSE OF STEROID TABLETS

Rescue courses of oral steroids may be needed to control exacerbations of asthma at any step. Indications include:(i) (ii) (iii) (iv) (v) (vi) Symptoms and peak expiratory flow (PEF) progressively getting worse day by day PEF falls below 60% of patients best Sleep is frequently disturbed by asthma Morning symptoms persist until midday despite usual treatment Diminishing response to inhaled bronchodilators Emergency treatment with nebulised or injected bronchodilators is required

Method
Give 30-60 mg of prednisolone immediately. This daily dose can be tapered off over a period of 7-14 days or stopped abruptly. It is necessary to review the adequacy of the patients usual medications.

11.

FOLLOW-UP AND MONITORING

Follow-up and monitoring include review of symptoms and measurement of lung function. PEF monitoring at every visit along with review of symptoms helps in evaluating the patients response to therapy and adjusting treatment (step-up or step-down) accordingly. PEF consistently > 80% of the patient's personal best suggests good control. Regular visits (at 1 to 6 month interval as appropriate) are essential even after control of asthma is established. At each visit review the following questions: 1) Is the asthma management plan meeting the expected goals? 2) Is the patient using inhalers, spacers or peak flow meter correctly? 3) Is the patient compliant to the medication and avoiding triggers? 4) Does the patient have any concern?

14

12.
12.1

MANAGEMENT OF ASTHMA IN PREGNANCY

Introduction

In general, during pregnancy, asthma becomes worse in a third of women, is stable in another third and improves in the remaining third50. Women should be reassured that their asthma medication carries less risk to the foetus than a severe asthma attack. Inadequately treated asthma can cause maternal and foetal hypoxaemia, which leads to complications during pregnancy and poorer birth outcomes. Poorly controlled asthma is associated with an increased incidence of low birthweight and premature babies, neonatal hypoxia, complications during labour, and perinatal and maternal mortality51-54. Hyperemesis gravidarum, maternal haemorrhage and pre-eclampsia are more common in this group51. 12.2 Management

The management of asthma during pregnancy is similar to that at any other time: treatment should be aggressive, with the aim of eliminating symptoms and restoring and maintaining normal lung function. Cooperation between the respiratory physician and obstetrician is important throughout pregnancy for women with severe asthma. Beta2-agonists: There is no evidence of a teratogenic risk with the commonly used inhaled beta2-agonists salbutamol, terbutaline and fenoterol. Delayed labour does not occur with bronchodilators administered by metered-dose inhaler or nebulisation. Ipratropium bromide: It appears to be safe for use during pregnancy, as it is poorly absorbed when administered by the inhaled route. Salmeterol/formoterol: These long-acting agents have not been tested extensively in pregnant women. Theophyllines: They may aggravate the nausea and gastroesophageal reflux suffered by some pregnant women and can cause transient neonatal tachycardia and irritability55,56. Teratogenicity has been shown in animals57,58 and there are occasional case reports of cardiovascular abnormalities in humans59. However, larger human studies have not shown any significant increase in foetal abnormalities60,61. Theophylline metabolism may be altered during pregnancy leading to increased serum levels62.

15

Sodium cromoglycate: This drug appears to have no adverse foetal effects. Inhaled corticosteroids: Inhaled corticosteroids are the mainstay of treatment in persistent asthma and appear to have a good safety profile in pregnancy. Although beclomethasone is a known animal teratogen, its use in pregnant women has not been associated with teratogenicity. The largest human experience of inhaled corticosteroids is with beclomethasone and it is therefore the inhaled steroid of choice in pregnancy63,64. Experience with fluticasone in pregnancy is limited. Oral corticosteroids: These are sometimes necessary for severe asthma in pregnancy but usually only for short periods. An increased risk of cleft palate has been reported in animals given huge doses of oral steroids65,66. The results of animal studies should not deter the practising clinician from using oral corticosteroids if required. Anti-leukotrienes: No data is available on the use of this agent in pregnant women. 12.3 Labour

Women with very severe asthma may be advised to have an elective caesarean section at a time when their asthma control is good. Symptoms of asthma during labour are generally easily controlled with standard asthma therapy. 12.4 Breastfeeding

Breastfeeding should be continued in women with asthma. Breast milk may contain very small amounts of the drugs used to treat asthma, but, in general, these are not known to be harmful to the infant. Corticosteroids are about 90% protein bound in the blood and are not secreted into breast milk in any significant quantity. Less than 1% of maternal theophylline is transferred to the infant67. In general, asthma medications are safe during pregnancy and lactation and the benefits outweigh any potential risks to the foetus and baby.

16

13.

GUIDELINES FOR THE MANAGEMENT OF ACUTE ASTHMA IN ADULTS

The presentation of a patient with acute asthma requires rapid assessment of its severity so that the appropriate treatment can be instituted. Although an acute severe attack of asthma may occasionally develop within a few minutes or hours, it usually occurs against a background of long term poorly controlled asthma that has been worsening for some days or weeks. The severity of acute asthma attacks is usually underestimated by patients, their relatives and their doctors, mainly due to failure to assess the condition objectively. Inadequate assessment of such attacks and inappropriate treatment with over reliance on bronchodilators and underuse of steroids contribute to morbidity and deaths2,3. 13.1 Aims of management

The aims of management are: 13.2 To prevent death To relieve symptoms To restore the patients lung function to the best possible level as soon as possible To prevent early relapse Assessment

The severity of the attack should be assessed by: 13.3 History Physical examination PEF measurement Features of mild asthma attack are: persistent cough increased chest tightness breathless when walking normal speech pulse rate < 100/min respiratory rate < 25 breaths/min moderate wheeze on auscultation, often end expiratory only PEF > 75% of predicted or best value SpO2 > 95% (on room air)

17

13.4 13.5 13.6

Features of moderately severe asthma attack are: breathless when talking talks in phrases pulse rate 100-120/min respiratory rate 25-30 breaths/min loud wheeze PEF between 50 to 75% of predicted or best value SpO2 91-95% (on room air) Features of very severe asthma attack are: breathless at rest talks in words pulse rate > 120/min respiratory rate > 30 breaths/min loud wheeze PEF < 50% predicted or best value68,69 SpO2 < 90% (on room air) Features of life-threatening asthma are: central cyanosis feeble respiratory effort silent chest on auscultation bradycardia or hypotension exhaustion confusion or unconsciousness or convulsion PEF < 30% predicted or best value (or a single reading of < 100L/min).

Arterial blood gas (ABG) tensions should be measured if a patient has any of the severe or life-threatening features. ABG markers of a severe life-threatening attack include: A normal (5-6 kPa, or 36-45 mm Hg) or high PaCO2 Severe hypoxaemia: PaO2 < 8 kPa (60 mm Hg) irrespective of treatment with oxygen A low pH

18

14.

MANAGEMENT OF ACUTE ASTHMA IN AN OUTPATIENT SETTING

(i) INITIAL PEF > 75% (Mild acute asthma) Give the patients usual inhaled bronchodilator or nebulised bronchodilator. Multiple doses (5-20 puffs) of inhaled bronchodilator using a large volume spacer can be given in place of nebulised bronchodilator70-72. Observe for 60 minutes. If the patient shows clinical improvement and PEF remains > 75%, discharge. Before discharge: review adequacy of usual treatment and step up if necessary according to guidelines for treatment of chronic persistent asthma ensure patient has enough supply of medications check and correct inhaler technique advise patient to return immediately if asthma worsens ascertain and address precipitating factors make sure that patient has a clinic follow-up appointment within 2 weeks

(ii) INITIAL PEF < 75% (this includes moderately severe to life-threatening asthma) Patients with more severe degrees of acute asthma should be managed as follows: Immediate treatment with: a) High concentration oxygen (> 40%) b) High doses of inhaled beta2-agonist (salbutamol 5 mg or terbutaline 5 mg or fenoterol 5 mg) in combination with anticholinergic (ipratropium bromide 0.5 mg)73-77 (Evidence A) should be administered via nebuliser driven by oxygen. If compressed air nebuliser is used, administration of supplemental oxygen should be continued. Alternatively, beta2-agonists may be given by multiple actuations of a pressurised aerosol inhaler into a large spacer device (2-5 mg, i.e. 20-50 puffs, five puffs at a time) preferably in combination with an anticholinergic. If there is poor response to inhaled bronchodilators, subcutaneous terbutaline or salbutamol 0.25-0.50 mg can be given.

19

c) Prednisolone tablets at 30-60 mg should be commenced immediately. If patient is unable to tolerate orally, intravenous hydrocortisone 200 mg stat or other forms of parenteral steroids should be given. High dose inhaled corticosteroids (2.4 mg budesonide daily in 4 divided doses) has been shown to achieve a relapse rate similar to 40 mg prednisone daily78. However, further studies are required to document the potential benefits of inhaled corticosteroids in acute asthma. NB: Sedatives should not be prescribed. Antibiotics are indicated only if there is evidence of bacterial infection. Chest radiograph should be done if pneumothorax or pneumonia is suspected.

Assessment of response to initial treatment

The response to treatment is monitored by: the patients symptoms physical findings measurement of PEF 15-30 minutes after initiating treatment

a) Good response to initial treatment The patient should: be relieved of dyspnoea have improved clinical status have a post bronchodilator PEF which is > 75% of predicted or best value

b) Incomplete response to initial treatment The patient has: persistent symptoms and signs post bronchodilator PEF which is 50-75% of predicted or best value

c) Poor response to initial treatment The patient has: persistent or deteriorating symptoms and signs a post bronchodilator PEF < 50% of predicted or best value

The subsequent management of patients with an initial PEF < 75% predicted or best value is summarised in Figure 1.

20

FIGURE 1 MANAGEMENT 30 MINUTES AFTER INITIAL TREATMENT OF ACUTE ASTHMA WITH AN INITIAL PEF < 75% PREDICTED OR BEST

Good response and PEF > 75% predicted or best value Observe for another 60 minutes If patient is stable or improving and PEF remains > 75%, DISCHARGE

Incomplete response and PEF 50-75% predicted or best value Repeat nebulised beta 2agonist and anticholinergic Observe for 60 minutes. 1)If PEF is still < 75%, ADMIT 2)If patient improves and PEF > 75%, DISCHARGE

Poor response and PEF <50% predicted or best value

ADMIT

NB: Patients requiring admission should preferably be accompanied by a nurse and/or a doctor.

Before discharge:
give prednisolone 30-60 mg daily for 7-14 days, plus regular inhaled steroids and inhaled beta2-agonist to be taken as needed review adequacy of usual treatment and step up if necessary according to guidelines for treatment of chronic persistent asthma ensure patient has enough supply of medications check inhaler technique and correct if faulty arrange for follow-up within 2 weeks advise patients to return immediately if asthma worsens

NB: Patients should be considered for admission if there is concern over the social circumstances such as patient staying alone and lack of transport for emergency visit to hospital.
If life-threatening features are present: Intravenous aminophylline 250 mg slowly over 20 minutes or intravenous terbutaline or salbutamol 0.25 mg over 10 minutes should be administered. The patient should be admitted immediately preferably to the intensive care unit and accompanied by a doctor. NB: Bolus intravenous aminophylline should not be given to patients already taking oral theophylline. 21

15.

SUBSEQUENT MANAGEMENT IN THE WARD

Continue oxygen > 40% Intravenous hydrocortisone 100-200 mg 6 hourly or prednisolone 30-60 mg daily Nebulised beta2-agonist 2-4 hourly preferably in combination with anticholinergic (it may be necessary to give nebulised beta2-agonist more frequently up to every 15 minutes)

If patient is still not improving, commence aminophylline infusion (0.5-0.9 mg/kg/ hour); monitor blood levels (where facility is available) if aminophylline infusion is continued for more than 24 hours. Terbutaline or salbutamol infusion at 3-20 mcg/ min after an initial intravenous bolus dose of 250 mcg over 10 minutes can be given as an alternative

In cases where response to the above treatment is inadequate, intravenous magnesium sulphate 2 g in 50 ml normal saline infused over 10-20 minutes may be given79

15.1 15.2 a) b)

Monitoring the response to treatment repeat measurement of PEF 15-30 minutes after starting treatment aim to maintain arterial oxygen saturation above 92% repeat arterial blood gas measurements if initial results are abnormal or if patient deteriorate monitor PEF at least 4 times daily throughout the hospital stay Other investigations Serum electrolytes, as hypokalaemia is a recognised complication of treatment with beta2-agonists and corticosteroids Electrocardiogram if indicated

Transfer patient to the intensive care unit or prepare to intubate if there is: deteriorating PEF worsening hypoxaemia, or hypercapnia exhaustion or feeble respiration confusion or drowsiness coma or respiratory arrest

22

16.

MANAGEMENT IN INTENSIVE CARE UNIT

continue with oxygen supplementation continue with intravenous hydrocortisone if the patient is mechanically ventilated, administer nebulised beta2- agonist with anticholinergic via the endotracheal tube. This can be given up to every 15-30 minutes

Intravenous aminophylline infusion or terbutaline or salbutamol infusion should be continued and magnesium sulphate infusion may be added.

17.

DISCHARGE PLAN FOR HOSPITALISED PATIENT

Before discharge, the patient should be: started on inhaled steroids for at least 48 hours in addition to a short course of oral prednisolone and bronchodilators stable on the medications he is going to take outside the hospital for at least 24 hours having PEF of > 75% of predicted or best value and PEF diurnal variability of < 20% able to use the inhaler correctly and if necessary, alternative inhaler devices could be prescribed educated on the discharge medication, home peak flow monitoring and self management plan (for selected, motivated patients), and the importance of regular follow up given an early follow-up appointment within 2-4 weeks for reassessment of the condition and for adjustment of the medicines

18.

MANAGEMENT OF ACUTE ASTHMA IN GENERAL PRACTICE

The clinic should preferably have facility for oxygen administration and equipment for resuscitation. The following are indications for immediate referral to hospital 1. 2. 3. Any life-threatening features Any features of a severe attack that persist after initial treatment PEF 15-30 minutes after nebulisation, which is < 50% of predicted or best value

Threshold for referral to hospital should be lowered for patients80: seen in the afternoon or evening rather than earlier in the day with previous severe attacks, especially if the onset of the current attack was rapid in whom there is concern over the social circumstances or relatives ability to respond appropriately
23

FIGURE 2 SUMMARY OF OUTPATIENT MANAGEMENT OF ACUTE ASTHMA

Assess asthma severity clinically and with PEF

Mild acute asthma PEF > 75% predicted/best

Moderate to severe acute asthma PEF < 75% predicted/best

Life threatening acute asthma PEF < 30% predicted/best

Give inhaled or nebulised beta2-agonist Give oxygen > 40% Give nebulised beta2-agonist or multiple puffs of MDI via a large Observe for 60 mins. If PEF > 75% and clinically improved, discharge patient Give oral prednisolone 30-60 mg or i.v. hydrocortisone 100-200 mg stat Give oral prednisolone 30-60 mg or i.v. hydrocortisone 100-200 mg stat spacer in combination with inhaled ipratropium Give oxygen > 40% Give nebulised beta2-agonist or multiple puffs of MDI via a large spacer in combination with inhaled ipratropium

Good response PEF > 75% and clinically improved

Incomplete response PEF 50-75% with persistent symptoms and signs

Poor response PEF < 50% with deteriorating or persistent symptoms and signs

Give i.v. aminophylline 250 mg slowly over 20 mins or i.v terbutaline/ salbutamol 0.25 mg over 10 mins. AND ADMIT patient to ICU. Do not give bolus aminophylline if patient is on oral

Observe for 60 mins. If PEF > 75% discharge patient*

Repeat nebulised beta2agonist and ipratropium Observe for 60 mins

Admit patient

PEF > 75%, discharge

PEF < 75%, admit

theophylline

NB: Before discharge ensure that patients treatment plan is reviewed, the medicine is adequate, the inhaler technique is correct, the appointment for review is given, and patient is advised to return if condition deteriorates. If patient was given steroids, continue with oral prednisolone for 7-14 days81-84.
24

Appendix 1
Example of a written asthma management plan
Name : Address :

Tel Numbers General Practitioner : Specialist : Ambulance : Hospital : Usual Medication : 1. 2. 3. 4.

Best Peak Flow Reading

L/min

25

YOUR ASTHMA IS WELL CONTROLLED IF:

You have no wheeze, shortness of breath nor cough You are able to do usual activities You sleep well You do not need your bronchodilator more than once a day Your peak flow is more than (80% of best)

You should continue your usual medications: (Preventer): (Reliever): Keep your appointment with your doctor.

YOUR ASTHMA IS UNCONTROLLED IF:

You notice wheeze and difficulty in breathing more than usual during the day Your usual activities are affected You wake up once or twice a night with asthma You need your bronchodilator more than 2 times a day Your peak flow is less than (80% of best)

You should increase the dose of

and consult your doctor as soon as possible.

YOUR ASTHMA IS SEVERE IF:

You notice wheeze and difficulty in breathing most of the day You are unable to carry out usual activities such as talking and walking You are awake most of the night You need your bronchodilator more than 6 times a day Your peak flow is less than (60% of best) inhaler and take tablets of

You should take 2-4 puffs of your reliever prednisolone (

mg) and seek immediate medical help.

26

Appendix 2
PEF normogram
HEIGHT
53 54
140

MALE

P.E.F.R. NOMOGRAM FOR ADULT CHINESE IN SINGAPORE (USE HEIGHT & AGE)
FEMALE
L/min
520 510

L/min
610

600

CM

INS
590

55 56 57 58

580

570 500 490 480 470 10 20 30 40 50 60 70 440 430 420 410 490 400 390 380 480 450 520 460 530 560

150

59 60 61 62

550

160

63 64 65 66

540

170

67 68 69 70

510

180

71 72 73

500

470

460

Regression Formula

Male PEF(L/min) - 72.1+9.8 H (ins) - 12 A (yrs) Female PEF(L/min) - 159+5 H (ins) - A (yrs) Male SD + 59.4 Female SD + 46.3

450

440

430

27

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The Revised 2002 Guidelines for Management of Adult Asthma is supported by educational grants from:

GlaxoSmithKline

The printing of this document is supported by an educational grant from: