MANAGEMENT OF ASTHMA

Dr M. Dikgang

Definitions

Chronic inflammatory disease of airways Increased responsiveness of

tracheobronchial tree Multiplicity of stimuli Episodic disease Narrowing of airways (acutely and

gradually), relieved spontaneously or after therapy.

Risk Factors(for development of asthma)

Risk Factors(for development of asthma)

INFLAMMATIONINFLAMMATION

Airway

Hyperresponsiveness

Airway

Hyperresponsiveness Airflow ObstructionAirflow Obstruction

Risk Factors(for exacerbations) Risk Factors(for exacerbations)

SymptomsSymptoms

Epidemiology Asthma is one of the most common chronic

diseases worldwide —160 million patients suffer from asthma

Prevalence increasing in many countries, especially in children — 1~4% in adult, 3~5% in children in China

A major cause of school/work absence An overall increase in severity of asthma

increases the pool of patients at risk for death

Worldwide Variation in Prevalence of Asthma Symptoms

International Study of Asthma and Allergies in Children (ISAAC)

Lancet 1998;351:1225

Aetiology

Genetic factorsEnvironmental factors

Mixed factorsAtopic

asthmaNon-atopic/idiosyncratic asthma

Late onsetEarly onset

Pathogenesis

Stimuli: Allergens (mites, fur, feathers,molds etc) Pharmacological (NSAIDS, B-blockers etc) Environmental (NO2, sulphur dioxide) Occupational (wood/vegetable

dust,pharmaceuticals etc) Infections (viruses-RSV, para-influenza) Exercise Emotional stress (vagal efferent activity,

endorphins)

Antigen PresentingCell

TH2

MastCell

Mediators

SurvivalActivation

AttractionAdhesion

Priming

Eosinophil

Endothelium

Ag:

Production

M I nman

BronchoconstrictionHyperresponsiveness

Pathology

Gross overdistention of lungs, non-collapsible

Gelatinous plugs of exudate in bronchial branches, down to terminal bronchioles

Hypertrophy of bronchial smooth muscle Hyperplasia of mucosal & submucosal

blood vessels Mucosal oedema Thickening of basement membrane Eosinophilic infiltrates in the bronchial

walls

Asthma Diagnosis

History and patterns of symptoms

Physical examination

Measurements of lung function

Measurements of allergic status to identify risk factors

Clinical Manifestation of Asthma

Recurrent episodes of wheezing Troublesome cough at night Cough or wheeze after exercise Cough, wheeze or chest tightness after

exposure to airborne allergens or pollutants Colds “go to the chest” or take more than 10

days to clear

Investigations

Lung function tests- FEV1/FVC ratio (<70%or normal), PEFR

Bronchodilator test- reversibility (>15% improvement in FEV1)

CXR Sputum (thick, with eosinophils +

Charcots-Leyden crystals), blood (IgE levels, eosinophilia)

Allergy tests- skin, inhalants, catecholamines etc.

COPD and Asthma are different diseases!

Asthma

cannot be fully prevented can be fully controlled

does not progress

COPD

can be preventedcannot be fully reversed

is progressive

COPD

Small airway narrowing

&Bronchospas

m&

Airway collapse

Maintain bronchodilatat

ion with regular

bronchodilator

COPD and Asthma are different diseases!

COPD&

Asthma(15%)

Control inflammation with ICS

Minimal bronchodilator

Allergic inflammation

of airways

Hyper-responsivenes

s

Bronchospasm

Asthma

History COPD AsthmaSmoker or ex-smoker

Nearly always Variable

Onset Usually > 40 years

Most < 30 years

Breathlessness Gradual and progressive

Paroxysmal

Chronic cough with sputum

Common Infrequent

Investigations

COPD Asthma

FEV1 Always reduced Variable

Daily variation in PEF

Minimal “Morning dip” + day-to-day

Reversibility <15% >15%

Treatment

GINA 2006: The goal of management

To effectively controll asthma by…

A. Suppressing and reversing inflammation

B. Treating bronchoconstriction and related symptoms

Managing Severe Asthma Exacerbations

Life-threatening medical emergencies

Treatment is often most safely undertaken in a hospital or hospital-based emergency department

Acute Asthma

Good Response

Observe for at least 1

hour

If Stable, Discharge to Home

Initial AssessmentHistory, Physical Examination, PEF or FEV1

Initial TherapyBronchodilators; O2 if needed

Incomplete/Poor Response

Add Systemic Glucocorticosteroids

Good Response

Discharge

Poor Response

Admit to Hospital

Respiratory Failure

Admit to ICU

Goals of Long-term Management

Achieve and maintain control of symptoms Prevent asthma episodes or attacks Maintain pulmonary function as close to normal

levels as possible Maintain normal activity levels, including

exercise Avoid adverse effects from asthma medications Prevent development of irreversible airflow

limitation Prevent asthma mortality

Components of Asthma Control

CharacteristicControlled (mild

intermittent)(All of the following)

Partly controlled (mild persistent)

(Any present in any week)

Uncontrolled (moderate-severe persistent)

Daytime symptomsNone (2 or less / week)

More than twice / week

3 or more features of partly controlled asthma present in any week

Limitations of activities

None Any

Nocturnal symptoms / awakening

None Any

Need for rescue / “reliever” treatment

None (2 or less / week)

More than twice / week

Lung function (PEF or FEV1)

Normal< 80% predicted or

personal best (if known) on any day

Exacerbation None One or more / year 1 in any week

Asthma Guidelines:Classes of Drugs

Preventers - anti-inflammatory

Relievers - short acting bronchodilators that provide rapid relief of

symptoms Controllers - sustained bronchodilator

action with unproven or mild anti-inflammatory

action

Classification of drugs used in the maintenance treatment of asthma

** Provisional categorisation pending further data

Inhaled corticosteroids

BeclomethasoneBudesonideFluticasoneFlunisolideTriamcinolone

Oral corticosteroidsPrednisonePrednisoloneMethylprednisolone

Anti-inflammatory

action to prevent asthma attacks

PREVENTERS

Long-acting ß2 agonists

SalmeterolFormoterol

Methylxanthines

Sustained-releasetheophyllines

Leukotriene receptor antagonists**

MontelukastZafirlukast

Sustained broncho-dilator action but weak or unproven anti-inflammatory effect

CONTROLLERS

Short-acting ß2 agonists

SalbutamolFenoterolTerbutalineHexoprenaline

OrciprenalineAnti-cholinergics

IpratropiumShort-acting

theophyllines

For quick relief of symptoms and use in acute

attacks as p.r.n. dose only

RELIEVERS

MILD INTERMITTENT SEVERE

Inhaledcorticostero

ids> 1000 µg/day(BDP

equivalent)+/-

Oral corticosteroid

s+/-

Long-acting ß2

agonist +/-SR

theophyllinesRefer pulmonologist

Inhaledcorticoster

oids500 - 1000

µg/day(BDP

equivalent)+

Long-acting ß2

agonist (preferred)

and/or SR

theophyllines

Inhaled corticosteroids

200 - 500 µg/day(BDP

equivalent)+

Long-acting ß2 agonist

(preferred) or SR theophyllines

orInhaled

corticosteroids 500 - 1000

µg/day (BDP equivalent)

Inhaled corticosteroi

ds200 - 500

µg/day(BDP

equivalent)ß2 agonists

prnß2 agonists

prnß2 agonists

prnß2 agonists

prnß2 agonists prn may

be required 4-6 x/day

Increasing Severity

LTRA? LTRA? LTRA

Pressurised Metered Dose Inhaler (pMDI)

A convenient and reliable multi-dose device

New propellant is HFA (ozone-friendly)

Rapidly moving, short-duration plume

Impaction of spray in oropharynx likely

Evaporating spray feels cold 70% of dose lodges in

pharynx and much may be swallowed, 15 -20% in lung

pMDIs: CORRECT USE

Remove mouthpiece cap

Shake inhaler (suspensions only)

Breathe out Place actuator

mouthpiece between lips Fire while breathing in

slowly and deeply Continue to inhale Hold breath (for 10 sec)

Errors with MDIs CRUCIAL ERRORS

Firing device at or after end of inhalation Stopping inhalation / inhaling through nose (“cold

Freon” effect) Bizarre errors (e.g. not removing mouthpiece cap)

NON-CRUCIAL ERRORS Firing device before start of inhalation Fast inhalation No breath-hold / short breath-hold Failure to shake inhaler (suspensions only)

SPACERS (HOLDING CHAMBERS): CORRECT USE

Useful for small children (used with snug-fitting face mask)

Useful in improving inhaled steroid deposition in those with difficulty co-ordinating firing of pMDI during or before inhalation

Shake inhaler (suspensions only) Insert pMDI into spacer Breathe out Fire while (or before) breathing in slowly

and deeply Continue to inhale Hold breath (for 10 sec) Repeat with second puff

DRY POWDER INHALERS

DRY POWDER INHALERS: CORRECT USE

Remove cover (device-specific) Prepare device / load dose (device-specific) Pierce capsule (single-dose devices only) Breathe out gently Place mouthpiece between lips Inhale deeply and quickly* Breath-hold (device-specific) Replace cover and store in dry cool environment

LEUKOTRIENE RECEPTOR ANTAGONISTS

Montelukast - SingulairZafirlukast - AccolateAdvantages:• Unique mode of action• Anti-inflammatory – no bronchodilator effect• Very simple dosing: taken by mouth; single dose strength for children, another for adults• Safe• Use:

– Add to inhaled corticosteroids– Monotherapy in mild allergic asthma (children)

Disadvantages:• Poor efficacy (not better than theophylline for most endpoints especially in adults( More useful in children)• Expensive !

NEBULIZERS – NOT recommended for regular use by asthmatics

ADVANTAGES Easy to use correctly

once prepared: relaxed tidal breathing

Convenient way of delivering high doses

Patients find them reassuring

Dose control possible in sophisticated devices

No propellants needed

DISADVANTAGES Bulky, inconvenient Electricity supply usually needed Preparation and assembly a problem, especially

for the elderly? Long treatment times Cleaning / contamination issues Expensive Patients rely on them instead of using controller

medications Their use can delay patients presenting to

emergency departments and lead to asthma deaths (false sense of security)

They are air and not oxygen-driven, so do not correct hypoxia

Misunderstanding about need for both long-term preventive and quick-relief medications

Difficulty with inhaler devices Fear of side effects or addiction Cost of medication Dislike of medication

Reasons for poor patient adherence to treatment

At regular visits (every one to six months): Monitor asthma control – Review symptoms

– Measure lung function – Assess compliance

Modify the treatment plan – Reinforce compliance

– Adjust medications

Follow-up

References

Kasper et-al. Harrison’s Principles of Internal Medicine, 16th edition: 2005; McGraw-Hill, New York, USA: pp1508-1516

Zhiwen Zhu. Pulmonary & Critical Care Medicine, 1st Affiliated Hospital of Sun Yat-Sen University, China