Chapter 82: Asthma

Asthma, which is an inflammatory disorder, is defined by the presence of both of the following:¹

• excessive variation in lung function (‘variable airflow limitation’, i.e. variation in expiratory airflow that is greater than that seen in healthy people)

• respiratory symptoms (e.g. wheeze, shortness of breath, cough, chest tightness) that vary over time and may be present or absent at any point in time

In young children in whom lung function testing is not feasible, including most preschool children, asthma is defined by the presence of variable respiratory symptoms.

Pathophysiology¹

Chronic asthma is an inflammatory disease with the following pathological characteristics:

• infiltration of the mucosa with inflammatory cells (especially eosinophils) and cellular elements

• airway hyper-responsiveness⁵

• intermittent airway narrowing (due to bronchoconstriction, congestion or oedema of bronchial mucosa or a combination of these) (see FIG. 82.1)

No single cause for asthma has been found, but a variety of factors may trigger an attack. These include specific factors such as viruses, allergens and non-specific factors such as temperature or weather changes and exercise. A checklist of trigger factors includes:

1. allergens—pollens, animal dander, dust mites, mould

2. bronchial infection

3. cold air, exercise

4. drugs—aspirin, NSAIDs, beta blockers

5. psychosocial problems, emotion—stress, laughter

6. food—sodium metabisulphate, seafood, nuts, monosodium glutamate

7. gastro-oesophageal reflux

8. hormones—pregnancy, menstruation

9. irritants—smoke, perfumes, smells

10. job—wood dust, flour dust, isocyanates, animals

Additional points

• Patients with asthma must never smoke.

• Atopic patients should avoid exposure to furred or feathered domestic animals if they have problems.

• About 90% of children with atopic symptoms and asthma demonstrate positive skin-prick responses to dust mite extract. Total eradication of house dust mite from the home is difficult.

Clinical features

The classic symptoms are:

• wheezing

• coughing (chronic, esp. at night)

• tightness in the chest

• breathlessness

Asthma is likely if more than one of the above is present. Other supporting features:

• symptoms recurrent or seasonal

• worse at night or early morning

• history of allergies

• family history of asthma or allergies

• widespread audible wheeze on chest auscultation

• symptoms rapidly relieved by a short-acting beta agonist bronchodilator (SABA)

Note: Asthma should be suspected in children with recurrent nocturnal cough and in people with intermittent dyspnoea or chest tightness, especially after exercise.

Severe symptoms and signs are presented in the section on dangerous asthma later in this chapter.

Examination⁶

Physical signs may be present if the patient has symptoms at the time of examination.

The absence of physical signs does not exclude a diagnosis of asthma as the chest examination may be normal between attacks. During an attack, auscultation usually reveals diffuse, high-pitched wheezes throughout inspiration and most of expiration, which is usually prolonged. If wheeze is not present during normal tidal breathing it may become apparent during a forced expiration or after asking the child to exercise for 1–2 minutes. Wheeze does not necessarily indicate asthma.

Absence of wheeze in a breathless person is a serious sign.

Investigations

• Spirometry: a value of <75% for FEV₁/VC ratio indicates obstruction (a relatively accurate test and recommended for those who can perform it, i.e. most adults and children >6 years; see CHAPTER 49)

• Measurement of peak expiratory flow rate (PEFR) or spirometry before and after SABA: has a characteristic improvement >15% in FEV₁ and PEFR

• Bronchial provocation tests: airway reactivity is tested in a respiratory laboratory to inhaled histamine, methacholine or hypertonic saline (rarely required, but sometimes useful to confirm diagnosis)

• Fractional exhaled nitric oxide test

• An exercise challenge may also be helpful

• Allergy testing may be appropriate

• Chest X-ray: not routine but useful if complications suspected or symptoms not explained by asthma

Reasons for suboptimal asthma control are presented in TABLE 82.1.

If inflammatory airways disease is undertreated there is the risk of fixed irreversible airways obstruction from submucosal fibrosis. One of the most common mistakes in medical practice is to fail to introduce inhaled corticosteroids for the management of patients with moderately severe asthma.

Patients with moderate to severe chronic asthma require regular measurement of PEFR, which is more useful than subjective symptoms in assessing asthma control. This allows the establishment of a baseline of the ‘patient’s best’, monitors changes, and allows the assessment of asthma severity and response to treatment.

Spirometry including FEV₁ is the gold standard (see CHAPTER 49). Peak flow meters are not a substitute for spirometry. There is considerable variation between users and instruments. However, they have a place in helping patients self-manage their asthma by serially recording their PEFR and comparing this with the best peak flow.

Large volume spacers

Some people who have trouble using metered dose inhalers (MDIs) can have a spacer fitted onto the mouthpiece of the inhaler. One puff at a time is put in the spacer. The patient breathes in from its mouthpiece, taking 1–2 very deep breaths, or 4–6 normal breaths (especially in children). This method is useful for adults having trouble with the MDI and for younger children (older than 3 years). Spacers are very efficient, overcome poor technique and cause less irritation of the mouth and throat (see FIG. 82.2).

They allow increased airway deposition of inhalant and less oropharyngeal deposition.

Note: It is recommended to dip plastic spacers into water with ordinary household detergent and dry in sunlight (no rinsing, no wiping) every 10 days or at least monthly.

Small volume spacers

Children under 5–6 years and/or 20 kg can use an MDI and a small volume valved spacer (AeroChamber, Breath-A-Tech) with a face mask.

Starting treatment¹

• Confirm the diagnosis.

• Assess recent asthma control and risk factors (see TABLE 82.2).

• Choose initial treatment appropriate to the above.

• Avoid the use of LABA on its own (i.e. without ICS), as it is associated with an increased risk of asthma death.

• Document evidence (patient’s notes).

• Identify management goals in collaboration.

• Provide clear written patient information.

• Educate and review regularly.

Goals of management:

• absent or minimal daytime symptoms and no nocturnal symptoms; restore normal airway function (>80% of predicted)

• maintain best possible lung function at all times—keep asthma under control

• reduce morbidity

• control asthma with the use of regular anti-inflammatory medication and relieving doses of β₂-agonist when necessary

Long-term goals:

• achieve use of the least drugs, least doses and least side effects

• reduce risk of fatal attacks

• reduce risk of developing irreversible abnormal lung function

Good asthma control

• minimal symptoms day and night

• no nocturnal waking due to asthma

• no limitation of normal activity or exercise

• minimal need for reliever medication

• no exacerbation

• normal or near-normal lung function (FEV₁ and/or PEFR >80% of predicted or best)

• no side effects of medication

Questions to assess asthma control¹

Ask about:

• limitation of daily activities

• shortness of breath

• sleep disturbance

• use of reliever medication

• perceived level of asthma control

It is useful to teach patients the concept of the ‘preventer’ and the ‘reliever’ for their asthma treatment. The pharmacological treatment of asthma is summarised in TABLE 82.3.

‘Preventer’ drugs: anti-inflammatory agents

These medications are directed towards the underlying abnormalities—bronchial hyper-reactivity and associated airway inflammation. Treatment with a ‘preventer’ is recommended if asthma episodes are >3/week or those who use SABA >3 times a week.

Corticosteroids

Inhaled (ICS)

Types:

• beclomethasone

• budesonide

• ciclesonide (single daily dose)

• fluticasone

Dose range:

• 400–1600 mcg (adults); aim to keep below 500 mcg children and 1000 mcg (adults)

Availability:

• MDI

• Turbuhaler

• Autohaler

• Accuhaler

Frequency:

• once or twice daily (helps compliance)

Side effects:

• oropharyngeal candidiasis, dysphonia (hoarse voice)—less risk with once daily ciclesonide

• bronchial irritation: cough

• adrenal suppression (doses of 2000 mcg/daily; sometimes as low as 800 mcg)

Note: Rinse mouth with water and spit out after using inhaled steroids.

ICSs have a flat dose–response curve so it may not be necessary to prescribe above ICS doses considered high—beclomethasone or budesonide 1000 mcg/day or fluticasone 500 mcg/day. For newly diagnosed patients with mild-to-moderate asthma ‘start low and step up prn’ (e.g. 250–400 mcg/day).⁶ Step down the dose when safe to do so.

Note: Most adults and older adolescents with asthma should be on long-term inhaled corticosteroid therapy.¹

Oral

Prednisolone is used mainly for exacerbations. It is given with the usual inhaled corticosteroids and bronchodilators.

Dose:

• up to 1 mg/kg/day (usual max. 50 mg) for 3 days to 2 weeks

Side effects:

• these are minimal if drug is used for short periods

• long-term use has significant side effects: osteoporosis, glucose intolerance, adrenal suppression, thinning of skin and easy bruising

Note: Short-term oral corticosteroids can be ceased abruptly.

Cromolyns

These are sodium cromoglycate (SCG) and nedocromil sodium. SCG is available as dry capsules for inhalation, metered dose aerosols and a nebuliser solution. They are often inhaled via a spacer in children. Adverse effects are uncommon; local irritation may be caused by the dry powder. Systemic effects do not occur.

Nedocromil is used for frequent episodic asthma in children over 2 years of age for the prevention of exercise-induced asthma and the treatment of mild-to-moderate asthma in some adults. The initial dose is 2 inhalations qid. Adverse effects are uncommon.

Leucotriene antagonists

These drugs, which include montelukast and zafirlukast, are very useful for seasonal asthma and aspirin-sensitive asthma and reduce the need for inhaled steroids or offer an alternative for those who cannot tolerate ICSs or have trouble using an inhaler. Favourable evidence is based on a small number of trials only, mostly in children but some adults benefit.⁹ Montelukast is taken as a 5 or 10 mg chewable tablet once daily.

Indications for preventive therapy¹⁰

Guidelines for introducing preventive asthma therapy in adults and children include any of the following:

• requirement of β₂-agonist >2 days per week or >1 canister every 3 months (excluding pre-exercise)

• symptoms (non-exercise) >2 times per week between attacks

• any symptoms during the night or on waking

• spirometry showing reversible airflow obstruction during asymptomatic phases

• asthma significantly interfering with physical activity despite appropriate pre-treatment

• asthma attacks ≥twice per month

• infrequent asthma attacks but severe or life-threatening

‘Reliever’ drugs or bronchodilators

The three groups of bronchodilators are:

• the β₂-adrenoceptor agonists (β₂-agonists)—short acting (SABA) and long acting (LABA)

• methylxanthines—theophylline derivatives

• anticholinergics

β2-agonists

These drugs stimulate the β₂ adrenoreceptors and thus relax bronchial smooth muscle. Inhalation is the preferred route of delivery; the vehicles of administration include metered dose inhalation, a dry powder, and nebulisation where the solution is converted to a mist of small droplets by a flow of oxygen or air through the solution.

Oral administration of β₂-agonists is not required. The inhaled drugs produce measurable bronchodilation in 1–2 minutes and peak effects by 10–20 minutes. The traditional agents such as salbutamol and terbutaline are short-acting preparations. The new longer-acting agents (LABA) include salmeterol, eformoterol and vilanterol.

These are to be used in combination with an ICS, not as monotherapy.¹¹

Theophylline derivatives

These oral drugs may have complementary value to the inhaled agents but tend to be limited by side effects and efficacy.

Anti-IgE monoclonal antibodies

These newer agents (e.g. omalizumab) bind IgE without activating mast cells. They are directed for use in patients >12 years of age with moderate to severe allergic eosinophilic asthma who have been treated by ICS and who have raised serum IgE levels. They are given by SC injection.

Antibiotic use for chronic asthma¹²

Antibiotics are not recommended apart from clinical evidence of super-respiratory infection. However, a recent Australian study concluded that ‘adults with persistent symptomatic asthma experience fewer exacerbations and improved quality of life when treated with oral azithromycin (500 mg tds) for several weeks’. Its clinical use remains uncertain.

Starting treatment

Current treatment supports the initial treatment (summarised in TABLE 82.2) of a SABA with low to moderate doses of ICS with estimated equivalent doses shown in the table.

Initiate therapy sufficient to achieve best lung function promptly.

Wean inhaled corticosteroids to the minimum dose needed to maintain adequate asthma control.

Prophylactic agents

This term is reserved for those medications that are taken prior to known trigger factors, particularly for exercise-induced asthma.

Exercise-induced asthma (options)

• β₂-agonist inhaler (puffer): two puffs 5 minutes immediately before exercise last 1–2 hours. LABA such as salmeterol and eformoterol are more effective if used with ICS.

• SCG or nedocromil, two puffs

• Combination β₂-agonist + SCG (5–10 minutes beforehand)

• Montelukast 10 mg (less in children ≥2 years) oral daily or 1–2 hours beforehand

• Paediatricians often recommend a non-drug warm-up program as an alternative to medication.

Ongoing management

The three-step asthma control plan^13,14

The National Asthma Council of Australia has developed the following follow-up plan, summarised in FIGURE 82.3.

Step 1: Assess asthma symptom control and identify the patient’s risk factors.

• Assess asthma symptom control over the previous 4 weeks.

• Assess the patient’s risk factors.

• Exclude factors contributing to poor control before intensifying preventer treatment:

  • – check adherence

  • – check inhaler technique

  • – check inhaler device is appropriate

  • – consider that symptoms may be due to alternative or comorbid diagnoses

Step 2: Treat and adjust to achieve good control.

• All patients should have a reliever inhaler for as-needed use.

• Most patients can achieve well-controlled asthma with low-dose ICS.

• Trial low-dose ICS before ICS/LABA fixed combination therapy¹⁵

• Reserve ICS/LABA as a later option. This combination is too readily used in Australia.

• Where appropriate, step down treatment.

• Schedule follow-up visit.

See TABLE 82.3.

Step 3: Review response and monitor to maintain control.

• Review diagnosis and treatment regularly.

• Monitor to maintain control.

A general management plan for chronic asthma is summarised in FIGURE 82.4.

Correct use of the asthma MDI (puffer)

Did you know that:

• faulty inhaler technique occurs in at least one-third of users?

• in faulty technique, up to 90% of the medication sticks to the mouth and does not reach the lungs?

• it is the inhalation effort—not the pressure from the aerosol—that gets the medication to the lungs?

• it is important to instruct patients properly and check their technique regularly?

The two main techniques

The open-mouth technique and the closed-mouth technique are the main methods, and both are effective but the closed-mouth technique is preferred. Both techniques are suitable for most adults. Most children from the age of 7 can learn to use puffers quite well.

The closed-mouth technique

See FIGURE 82.5.

Instructions for patients:

1. Remove the cap. Shake the puffer vigorously for 1–2 seconds. Hold it upright (canister on top).

2. Place the mouthpiece between your teeth (do not bite it) and close your lips around it.

3. Breathe out slowly and gently to a comfortable level.

4. Tilt your head back slightly with your chin up.

5. Just as you then start to breathe in (slowly) through your mouth, press the puffer firmly, once. Breathe in as far as you can over 3–5 seconds. (Do not breathe in through your nose.)

6. Remove the puffer from your mouth and hold your breath for about 10 seconds; then breathe out gently.

7. Breathe normally and then repeat the inhalation if you need to.

Extra points

• The usual dose of standard MDI is one or two puffs (adult) every 3–4 hours for an attack (four puffs in children).

• If you do not get adequate relief from your normal dose, contact your doctor.

• It is quite safe to increase the dose, such as to 4–6 puffs.

• If you are using your inhaler very often, it usually means your other asthma medication is not being used properly. Discuss this with your doctor.

Autohaler

The Autohaler is a breath-activated MDI which can improve lung deposition in patients with poor inhaler technique.

The Turbuhaler

The Turbuhaler is a dry powder delivery system that is widely used as an alternative to the MDI. It is a breath-activated device.

Other dry powder devices are the Accuhaler and Diskhaler.

Spacers versus nebulisers

Both MDIs via a spacer and dry powder inhalers are at least as effective as a nebuliser for treating acute exacerbations in both adults and children.¹⁶ They are considerably cheaper and more readily available than an electrically powered device.

Failure to recognise the development of a severe attack has cost the lives of many asthmatics. A severe attack can start suddenly (even in mild asthmatics) and catch people by surprise.

High-risk patients

People who have experienced one or more of the following are more likely to have severe attacks:

• previous severe asthma attack

• previous hospital admission, especially admission to intensive care

• hospital attendance in the past 12 months

• long-term oral steroid treatment

• carelessness with taking medication

• night-time attacks, especially with severe chest tightness

• recent emotional problems

• frequent SABA use

Early warning signs of a severe asthma attack:

• symptoms persisting or getting worse despite adequate medication

• increased coughing and chest tightness

• poor response to two inhalations

• benefit from inhalations not lasting 2 hours

• increasing medication requirements

• sleep being disturbed by coughing, wheezing or breathlessness

• chest tightness on waking in the morning

• low PEFR readings

Thunderstorm asthma¹⁷

One theory is that this occurs when the high winds preceding a storm whip up massive quantities of rye grass pollens which absorb moisture and rupture, releasing allergens. People most vulnerable to an asthma attack are those with a history of allergy and poorly controlled asthma in particular. When an attack is imminent, at-risk people should stay inside with windows and doors closed, take preventer medication, follow action plans and ensure reliever drugs are readily available. Treatment is with a salbutamol spray followed by corticosteroids.

Seasonal allergic rhinitis patients not on constant intranasal corticosteroids (INCS) should start taking them 6 weeks before the pollen season and continue until pollen levels abate. For those with asthma include a combination of an INCS and intranasal antihistamine if symptoms are severe or not controlled by INCS alone.¹

Dangerous signs

• Marked breathlessness, especially at rest

• Sleep being greatly disturbed by asthma

• Asthma getting worse quickly rather than slowly, despite medication

• Feeling frightened

• Difficulty in speaking; unable to say more than a few words

• Pulsus paradoxus

• Exhaustion and sleep deprivation

• Drowsiness or confusion

• Chest becoming ‘silent’ with a quiet wheeze, yet breathing still laboured

• Cyanosis

• Chest retraction

• Respiratory rate greater than 25 (adults) or 50 (children)

• Pulse rate >120 beats/min

• Peak flow <100 L/min or <40% predicted FEV₁

• Oximetry on presentation (SaO₂) <90%

Asthma action plans

Examples of action plans for patients are presented below. Having a written asthma action plan as part of self-management reduces asthma-related mortality and morbidity.¹⁸

Action plan

If you are distressed with severe asthma:

• call an ambulance and say ‘severe asthma attack’ (best option)

  or

• call your doctor

  or

• if you are having trouble finding medical help, get someone to drive you to the nearest hospital

Follow the ‘4 × 4 × 4’ plan with your reliever medication, but keep using it continuously if you are distressed.

The following is an example of an asthma action plan that the patient keeps on a card for easy reference. Remember to have extra prednisolone and salbutamol in a household where you may be staying.

The acute severe asthma attack

Summary (adult dosage):^6,8

• continuous nebulised salbutamol (or terbutaline) with oxygen flow rate 6–8 L/min if nebuliser available (or 12 puffs of β₂-agonist inhaler, with spacer, using one loading puff at a time followed by 4–5 normal tidal breaths)

Ipratropium bromide may be mixed with β₂-agonist for concurrent nebulisation.

• parenteral β₂-agonist (e.g. salbutamol 500 mcg IM, SC)

• corticosteroids, e.g. prednisolone 50 mg (o) statim then daily until resolved

  or

• hydrocortisone 250 mg IV or IM, 6 hourly

• oxygen 8 L/min by face mask to maintain SpO₂ >92–95% or at least 95% in children

• monitor PEFR

Further deterioration:

• magnesium sulphate 25–100 mg/kg (max. 2 gm) IV over 20 min

• adrenaline 0.5 mg 1:1000 SC, IM or 1:10,000 IV

The prevalence of asthma is increasing in childhood and the management (especially in infants) is always a concern for the family doctor. The aim of treatment is to enable children to enjoy a normal life, comparable with that of non-asthmatic children, with the least amount of medication and at minimal risk of adverse events. Maintenance should be determined by symptom control and lung function, especially using clinical criteria since PEFR is unreliable. A diagnosis of asthma should not be made if cough is the only or predominant symptom and no signs of airflow limitation.

Key checkpoints

• Seek specialist advice for children under 6 months of age.

• Bronchodilators, inhaled or oral, are ineffective under 12 months.

• The delivery method is a problem in children and TABLE 82.4 gives an indication of what systems can be used at various levels.

• In the very young (e.g. 1–2 years old), a spacer with a face mask such as Aerochamber or Breath-A-Tech can deliver the aerosol medication.

• The PEFR should be measured in all asthmatic children older than 6 years. Children under 6 years generally cannot cope with the meters and those with mild asthma don’t usually need PEFR measurement.

• The Turbuhaler is usually not practical under 7–8 years.

Prophylaxis in children

The non-steroidal medications, montelukast (oral) and SCG and/or nedocromil sodium by inhalation, are the prophylactic drugs of choice in childhood chronic asthma of mild-to-moderate severity.

If there is no clinical response to these agents in 4 weeks, consider use of inhaled corticosteroids, but the risks versus benefits must always be considered. Any dose equal to or greater than 400 mcg in children can have side effects, including growth suppression and adrenal suppression. Aim for a maintenance of 100–400 mcg, which keeps the child symptom-free. Once this stage is reached, consider stopping treatment or changing to the non-steroidal options.

Leucotriene antagonists taken orally for children aged 6 years and above is another option.

Delivery systems for children are presented in TABLE 82.4. Guidelines for the management of asthma in children are summarised in TABLE 82.5.

• If you are doubtful about the diagnosis

• For problematic children

• For advice on management when asthmatic control has failed or is difficult to achieve

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Asthma

• Asthma: correct use of your aerosol inhaler

• Asthma: dangerous asthma