bronchial asthma respiratory disorders. asthma is a common & chronic inflammatory condition of...

Bronchial Asthma

Respiratory Disorders

Asthma is a common & chronic inflammatory condition of the airway.

Cause is not completely understood.

Common symptoms are caused by hyperresponsive airways.

Key Points

Symptoms include coughing, wheezing, chest tightness & shortness of breath.

The only reliable, simple & objective way to diagnose asthma is to demonstrate airflow limitation.

Key Points (Contd.)

Asthma triggers should be avoided or controlled.

Pharmacological therapy should involve easily anti-inflammatory treatment in all but the mildest asthmatics.

Key Points (Contd.)

Optimum treatment involves –the lowest doses of therapy

that provide good symptom control with minimal or no side effects

Key Points (Contd.)

Which is the best drug delivery device? the one that patient can use

correctly. Why asthma control proves

difficult? Poor compliance & Poor inhaler technique

Key Points (Contd.)

Patients must be educated to take an active role in their

disease managementbe given individualized self

management plans & be regularly supervised by the

health care team

Key Points (Contd.)

Asthma means ‘panting’ (breathless). It is a broad term used to refer to a

disorder of the respiratory system that leads to episodic difficulty in breathing.

It is a chronic (long-term) lung disease that inflames and narrows the airways.

Definition

What are the symptoms?wheezing, coughing, chest tightness, and shortness of breath.

Symptoms

It has been estimated that about 4% of the British & American populations have asthma.

Mortality from asthma is estimated at approximately 0.4 per 100000. Common reason for death is thought to be inadequate assessment of the severity of airway obstruction by the patient & clinician.

The probability of children having asthma-like symptoms is estimated to be between 5% & 12%, with a higher occurrence in boys than girls & in children whose parents have an allergic disorder.

The specific abnormality underlying asthma is hyperreactivity of the lungs to one or more stimuli.

This can also occur in certain patients with chronic bronchitis & allergic rhinitis but usually to a

lesser extent.

Aetiology

There are a number of trigger factors.

The role of occupation in the development of asthma has become apparent with increased industrialization.

Aetiology (Contd.)

Bronchial reactivity may persist for years after exposure to the trigger factor.

Drug-induced asthma may be severe, & the most common causes are β- blocker drugs & prostaglandin synthase inhibitors.

The administration of β adrenoceptors blockers to a patients can cause β2 receptor blockade & consequent bronchoconstriction.

Aetiology (Contd.)

Aspirin & related NSAID inhibit the enzyme cyclo-oxygenase, which normally converts arachidonic acid to prostaglandins.

When this pathway is blocked an alternative reaction predominates, leading to an increase in production of bronchoconstrictor leukotrienes.

Aetiology (Contd.)

• Asthma episodes can be triggered by a variety of factors, most notably:

• allergens, • infections, • environmental pollutants or • non-specific stimuli such as

– exercise and – emotional states.

• Between 50 and 70 per cent of adults with asthma suffer from allergies.

Trigger Factors

• Most common trigger in Children under 3 years?

• Viral infections are likely to be the most common trigger.

• After 3 years, allergies also begin to play an increasing role as a trigger.

Trigger Factors (Contd.)

• After 20 years of age ––occupational exposure to toxic

substances and –allergens also can beimp

triggers for asthma.

Trigger Factors (Contd.)

Extrinsic asthma: Common in children, associated with a genetic predisposition, & is precipitated by known allergens.

Pathophisiology

Intrinsic asthma: Tends to develop in adulthood, & symptoms are triggered by non-allergic factors.

Pathophisiology (Contd.)

What are the non-allergic factors?viral infection, irritants which cause epithelial damage

& mucosal inflammation, emotional upset which mediates

excess parasympathetic input or exercise which causes water & heat

loss from the airways, triggering mediator release from mast

cells.

Pathophisiology (Contd.)

Histamine & other mediators of inflammation are released as a result of an IgE-antibody-mediated reaction on the surface of the mast cell.

They attract eosinophils & neutrophils.Histamine triggers rapid

bronchoconstriction whereas leukotriens such as LTC4, LTD4 & LTE4 constrict at a slower rate.

Pathophisiology (Continued…)

The chemotactic agents cause a slower reaction characterized by the infiltration of marcophages into the lumen of the airways.

Macrophages release prostaglandins, thromboxane & platelet-activating factor (PAF).


PAF appears to sustain bronchial hyperreactivity & cause respiratory capillaries to leak plasma, which increases mucosal oedema.

It also facilitates the accumulation of eosinophils within the airways, a characteristic pathological feature of asthma.


Eosinophils release various inflammatory mediators such as LTC4 & PAF.

Epithelial damage results & thick viscous mucus is produced that causes further deterioration in lung function.

In asthma patients there is an increase in the size of bronchial glands & goblet cells that produce mucus.


Most commonly asthma is described as a recurrent episodes of difficulty in breathing (dyspnoea) associated with wheezing.

Diagnosis is usually made from the clinical history from the patient or patient’s representative confirmed by demonstration of reversible airflow obstruction, with repeated measures of lung function.

Clinical Manifestations

Tightness of the chest, shortness of breath & abnormal lung function tests that improve by 15% with administration of suitable treatment confirm the diagnosis of asthma.


Acute Severe Asthma:It is a dangerous condition that

requires hospitalization & immediate emergency treatment.

It occurs when brochospasm has progressed to a state where the patient is breathless at rest & has a degree of cardiac stress.


Acute Severe Asthma:The breathlessness with a peak flow rate

< 100 litre/minute, is severe that the patient cannot talk or lie down.

It can increase the pulse rate to more than 110 beats/minute.

It leads to low arterial oxygen tension (PaO2) with the patient becoming fatigued, cyanosed, confused & lethargic.

Also the arterial CO2 (PaCO2) tension is low.


The most useful test for abnormalities in airway function is the Forced Expiratory Volume (FEV).

The patient inhales deeply as possible & then exhales forcefully & completely into a mouthpiece connected to a spirometer.

The FEV1 is a measure of the forced expiratory volume in the first second of exhalation.

Investigations

Another volume that is commonly measured is the forced vital capacity (FVC).

FVC is an assessment of the maximum volume of air exhaled with maximum effort after maximum inspiration.

The FEV1 is usually expressed as a percentage of the total volume of air exhaled, & is reported as the FEV1/FVC ratio.

Investigations (Contd.)

Normal individuals can exhale at least 75% of their total capacity in 1 second.

Any reduction indicates a deterioration in lung performance.

The peak flow meter is a useful means of self assessment for the patient.

It measures Peak Expiratory Flow Rate (PEFR).

PEER is the maximum flow rate that can be forced during expiration.


Asthma Treatment Since Asthma involves

inflammation and bronchoconstriction,

Treatment should be directed towards –Reducing inflammation andIncreasing bronchodilatation.


Restoration of normal airways function and prevention of severe acute attacks are the main goals of treatment.

Anti-inflammatory drugs should be given to all patients with all but the mildest of symptoms.


Other measures, such as avoidance of recognized trigger factors, may also contribute to the control of this disease.

The lowest, effective dose of drugs should be given to minimize short-term and long-term side effects.


However, it should always be remembered that asthma is a potentially life –threatening illness and is often under-treat.


• The pharmacological management of asthma depends upon the frequency & severity of a patient’s symptoms.

• Infrequent attacks can be managed by treating each attack when it occurs.

• But with more frequent attacks preventive therapy needs to be used.

Chronic Asthma

• The preferred route of administration of the agents used in the management of asthma is by inhalation.

• inhalation allows the drugs to be delivered directly to the airways in smaller doses and

• with fewer side-effects than if systemic or parenteral routes were used.


• Inhaled bronchodilators also have a faster onset of action than when administered systemically &

• give better protection from bronchoconstriction.

–β adrenoceptor agonists are the mainstay of the management of asthma.

–Selective β2 agonists such as salbutamol and terbutaline have now replaced the order,

–Non-selective agents such as •adrenalin (epinephrine),• Isoprenaline and•Orciprenaline.

β adrenoceptor agomist bronchodilators:

• The selective agents have fewer β1-mediated side-effects, particularly cardiotoxicity.

• However, β2 receptors are also present in myocardial tissue.

Bronchodilators (Contd.)

• Therefore, cardiovascular stimulation resulting in tachycardia and palpitations is still the main dose-limiting toxicity with these agents.

• The degree of selectivity varies with the agent, dose, route and duration of therapy.

Bronchodilators (Contd.)

–Regular anti-inflammatory treatment must be given to patients who require an inhaled bronchodilator regularly.

–The agents used include corticosteroids and cromones.

Inhaled anti-inflammatory agents:

–The threshold frequency of β2 agonist use, which prompts the start of this ‘preventer’ therapy, has not been fully established.

–A review of current evidence has concluded that the threshold should be the use of β2 agonists at an average of two or three times daily.

• At present, inhaled corticosteroids are the initial drugs of choice.

• Beclometasone or budesonide are used at doses of 100-400 micrograms twice daily.

• Higher doses are used if symtoms persist. • The dose of inhaled corticosteroid should be

reduced, if possible, once symptoms and peak expiratory flow rates have improved.

Inhaled anti-inflammatory agents:

• Aditional bronchodilators:–Aditional bronchodilators may be required

if symptom does not adequately controlled.• Inhaled anticholinergic agents:

–These block muscarinic receptors in bronchial smooth muscle and can be added to the treatment regimen.

– Ipratropium bromide 80 µg FOUR times daily or oxitropium 200 µg twice daily are available.

• anticholinergic agents have slower onsets of action than β2 agonists but last longer.

• The anticholinergics may be especially helpful in the elderly where asthma may be complicated by a degree of obstructive airways disease.

• Oral bronchodilators:–Either β2 agonists or theophylline can also

be added for additional symptom control.– Slow release forms should be used;– These are especially useful in a single night-

time dose if nocturnal symptoms are troublesome although twice daily dosing is more usual.

–Oral bronchodilators may also become necessary in patients who are unable to use inhaler therapy effectively.

–Theophylline should be started at a dose of 3 mg/kg/day in adults and increased after 7 days to 6 mg/kg/day.

Oral bronchodilators (Contd.)

–These are only considered if conventional doses do not achieve adequate symptom control.

–Nebulized drugs such as salbutamol 2.5-5 mg per dose are given.

Oral bronchodilators (Contd.)

–Multiple actuations of a metered-dose inhaler into a large volume spacer can be used instead of a nebulizer.

–Terbutaline has been given by subcutaneous infusion in the treatment of ‘brittle’asthma, where there is an unpredictable and rapid onset of airway narrowing, causing sudden onset of acute, severe life threatening asthma.

When Used???• If Symptom control can not be achieved with maximum doses of-

• Inhaled Bronchodilators• Steroids

How oral corticosteroids can be given???•Dose should be given as a-

• Single Morning Dose. •Why? To minimize adrenal suppression.Dose• Short courses of high-dose oral steroids, 30-60 mg, can be Safely Used during Exacerbations of Asthma

Oral Corticosteroids

Some agents are being investigated Why Investigated???• To reduce the Steroid Dose on Systemic Steroids Dependent

Patients. Which agents are being investigated??• Methotrexate• Ciclosporin• Gold Side effects• All these agents have Potentially Toxic Side-effects and

need to be Closely Monitored

Steroid- Sparing Agents

Long-acting inhaled β2 Agonists Salmeterol and Formoterol are available.

These agents should be used in conjunction with Conventional β2 Agonists, rather than as replacements, as the latter have faster onsets of action.

When Used???• If Low-dose Inhaled Steroids fail to control asthma

symptoms adequately, then Long-acting β2 Agonists can be added instead of increasing the Steroid Dose.

Long-acting β Adrenoceptor Agonist Bronchodilators

These agents can also be used-• to control Nocturnal and Early Morning Symptoms in

place of Oral Theophyllines • to manage Aspirin/ Non-steroidal-induced asthma

Note: In all instances they should be discontinued if no benefit is gained from their use.

Long-acting β Adrenoceptor Agonist Bronchodilators (Contd.)

What is the ideal way of treating an acute attack ?

• The ideal way of treating an acute attack is to educate patients to recognize when their condition is deteriorating so that they can initiate treatment to prevent the attack becoming severe. This can be achieved by an Individualized Self-Management Plan.

• Doses of inhaled β2 Agonist and Inhaled Corticosteroid Should be increased

• A Short Course of Oral Steroids commenced at a dose of 40-60 mg every morning for 1 week.

Prevention of Acute Attack (contd.)

If the condition deteriorates further??• Then Hospital Admission may become necessary.

This process should be Self-referral from the patient, responding to criteria drawn up by the Doctor, such as the Peak Expiratory Flow Rate (PEFR) falling to 100-150 liters/minute.

The education of patients and their relatives in the management of acute attacks should always stress the prompt initiation of further treatment and early referral.

Prevention of Acute Attack (contd.)

Where immediate management should be initiated?• The immediate treatment of acute severe asthma should

take place in the –• patient’s home• during the ambulance journey• or immediately on admission to hospital.

Whenever possible, Oxygen is administered in a high concentration, at high flow rates.

A nebulized β2 agonist is administered, which should give prompt bronchodilation lasting 4-6 hours

Immediate Management of Acute Severe Asthma

Nebulizers are used in preference to conventional inhalers because they permit a high dose (10-20 times the dose of a metered dose inhaler) and they require no coordination on the part of the patient between inspiration and actuation, which is helpful in those

Distressed or for those who panic.

Immediate Management of Acute Severe Asthma (contd.)

If a nebulizer is not immediately available ???• Then multiple actuations of a metered-dose inhaler

into a large volume spacing device is an acceptable alternative. Salbutamol is generally used at a dose of 2-5 mg (20-50 puffs).

Corticosteroids are also given in the acute attack. Oral prednisolone 0.6 mg/kg (commonly 40-60 mg) is the first line choice


If the Patient can’t take oral medication???• Then intravenous hydrocortisone 3-4 mg/kg

(commonly 200 mg) is given. This reduces and prevents the inflammation that

causes oedema and hypertension of mucus which helps to relieve the resultant smooth muscle spasm.


If life-threatening features are present???• Intravenous bronchodilators (ex. Intravenous

Aminophylline) can be used, if life-threatening features, such as

- cyanosis

- bradycardia

- confusion

- exhaustion

- or unconsciousness are present.


If the patient is already taking an oral theophylline??

• Then a β2 agonist such as salbutamol 200 micrograms over 10 minutes is often preferred.

If there is evidence of a bacterial infection??• Then Antibiotics are used.


• All patients should be monitored throughout their treatment with objective measures of their Peak Expiratory Flow Rates (PEFRs) before and after bronchodilator treatment.

• Continual monitoring of their arterial blood gas concentrations are done to ensure adequate oxygen is being given.

Subsequent Management of Acute Severe Asthma

Initially, β2 agonists are given every 4 hours and the corticosteroids given orally every morning or every 6 hours if intravenous treatment is required.

If the response to the initial treatment is good???• Then treatment is tailed off gradually. If the patient’s condition has not responded to

the initial treatment within 15-30 minutes???• Then nebulized ipratropium bromide 500

micrograms may be given together with each β2

agonist dose.

Subsequent Management of Acute Severe Asthma (contd.)

Intravenous aminophylline or intravenous β2

agonist is then added if progress is still unsatisfactory.

The choice between intravenous aminophylline and intravenous β2 agonist depends on concurrent therapy and side effects profiles.

Serious toxicity can occur with parenteral aminophylline, and patients must be carefully monitored for nausea and vomiting, the most comon early signs of toxicity.


Further deterioration in the condition may require assisted mechanical ventilation on an intensive care unit (ICU).

As the patient responds to treatment, infusion can be stopped and other treatment changed or tailed off as described above.

Note: Throughout the treatment program, potential drug interactions should be anticipated and managed appropriately.


Cornerstones of the management of asthma are

- correct use of drugs and

- the education of patients.

Patient Care

There are 3 main steps in the education of the asthmatic patient:

1. The patient should have an understanding of the action of each the medicines they use.

2. The appropriate choice of inhalation device(s) should be made and the patient educated to use them correctly.

3. An individualized self-management plan should be developed for each patient.

Patient Care (contd.)

Increasing the knowledge of patients about their asthma therapy is a necessary component of asthma management.

Education programs must look at modifying a patient’s behavior and attitude to asthma.

Patient Knowledge of Asthma Treatment

Counseling should lead to increased patient confidence in the ability to self-

manage asthma decrease hospital admission rates and emergency

visits by general practitioners increase compliance improve quality of life.

Patient Knowledge of Asthma Treatment (contd.)

Specific counseling on drug therapy should concentrate on 3 areas:

drugs used to relieve symptoms drugs used to prevent asthma attacks and those drugs which are given only as reserve

treatment for severe attacks.

Patient Knowledge of Asthma Treatment (contd.)

Choice of Inhalation Device is a vital point. The incorrect use of inhalers will lead to

suboptimal treatment. Several factors need to be considered when

choosing the appropriate device, including the- patient’s age severity of disease manual dexterity coordination and personal preference.

Choice of Inhalation Device

Advantages of Extension Devices :

They- allow greater evaporation of the propellant reduce particle size & velocity reduce oropharyngeal deposition increase lung deposition may reduce inhaled corticosteroids related

complications, like-oral candidiasis and dysphonia.

Metered-dose inhaler with a spacer extension

Spacers are useful for people who have poor coordination between inspiration and actuation.

Small volume spacer

Small volume spacer devices are available, either as an integral part of the design of some MDIs, as illustrated in figure, or as an addiction.

Fig: Spacer extension as integral part of metered- dose inhaler

Metered-dose inhaler with a spacer extension (contd.)

Some coordination between inspiration and inhalation is required for small volume spacer.

These are also more convenient to carry around than the larger spacers.

Large-volume spacers Large-volume spacers are available, and are more

efficient than the smaller spacers.

Fig: Large-volume spacers (Volumetric)


The volumetric and the Nebuhaler are two such devices. These have one-way inhalation valves that allow several inhalations of one dose from the spacer’s chamber.

No coordination is required between actuation of the MDI (Metered-dose inhaler) and inhalation.

This type of spacer has been shown to produce greater bronchodilation than either a conventional MDI or a nebulizer.


These are MDIs that are actuated automatically by inspiratory flow rates.

One type is illustrated in following figure.

Fig: Breath-actuated metered-dose inhaler.

This is easily managed by adults and children and eliminates the need for the correct coordination of inspiration and actuation.

Breath-actuated Metered-dose Inhalers

Several types are available. Advantages of dry Powder Inhalers:

These are freon propellant free easier to use than conventional MDIs useful for those who have difficulty coordinating

an MDI and can be used by children as young as 4 years old.

Dry powder inhalers are available as either single-dose, or multiple-dose devices.

Dry Powder Inhalers

A nebulizer produces an aerosol by blowing air or oxygen through a solution to produce droplets of 5 µm or less in size.

Nebulizers require little coordination from the patient as any drug is inhaled through a facemask or mouthpiece using normal tidal breathing.

Nebulizers are therefore useful in patients who are unable to use conventional inhalers.

For example children under 2 years old, patients with severe attacks of asthma unable to produce sufficient inspiratory effort and those lacking the coordination to use other inhalers.

Nebulizers

Nebulized bronchodilators can be used in acute severe asthma attacks.

Most of the β2 agonists, as well as ipratropium bromide, beclometasone, budesonide and sodium cromoglicate, are available for nebulization. The majority of these preparations are made up in isotonic 0.9% sodium chloride and are available in preservative-free, unit dose preparations.

Nebulizers (contd.)

The use of solutions that are either hypertonic or hypotonic, particularly after dilution with water, or contain a preservative such as benzalkonium chloride or EDTA, has been associated with bronchoconstriction.

Nebulizers (contd.)

The following points are critical for the correct use of a nebulizer:

1. Nebulizers should only be driven by compressed air or by oxygen at flow rates of at least 5-6 liter/min to ensure that droplets of the correct size are produced.

2. For all drugs a minimum volume of 3-4 ml should be nebulized, using 0.9% sodium chloride as a diluent if necessary.

Nebulizers (contd.)

Why minimum volume of 3-4 ml is required???

This volume is required to reduce the amount of drug that is unavoidably left in a ‘dead-space’ fluid volume of about 1 ml at the end of nebulization.

3. Most nebulizer chambers are disposable but will last 3-4 months when used by a patient at home. The chamber must be emptied after use and each day the chamber should be rinsed in hot water and dried by blowing air through the device. Several centres advocate that once a week the chamber should be sterilized using 0.02 % hypochlorite to prevent bacterial contamination. The chamber is thoroughly rinsed to remove all traces of hypochlorite and then dried.

Nebulizers (contd.)

4. The nebulizer should be serviced at least once a year.

5. Each patient should be given a self-management plan for the correct use of his/her nebulizer. If the nebulizer is only for use in severe attacks, the patient should be advised to use it only when the peak flow reading falls below a specified amount and not to exceed a maximum dose, e.g. 5 mg of salbutamol.

Caution: Patients must be informed that they should contact their doctor if the nebulizer fails to give the expected relief lasts for less than 4 hours.

Nebulizers (contd.)

Disadvantages of Nebulizers:

There may be over-reliance on the nebulizer by the patient which can result in a delay in seeking medical advice, while high doses of bronchodilators used increase the incidence of side effects.

Nebulizers (contd.)

Every asthmatic should be considered for an individualized self-management plan. These plans are a means of giving patients more confidence by involving them in the management of their own asthma.

The patient then should be able to deal with any fluctuation in their condition and know when to seek medical advice.

Supervised patient self-management has been shown to improve patient knowledge .

Self-management Plans

Supervised patient self-management has been shown to improve-

patient knowledge concordance and quality of life

and reduce asthma-related incidents such as days off work, whereas information-only education has shown no effect on health outcomes.

Self-management Plans (contd.)

Key elements of a self-management plan:

Key elements of a self-management plan include being able to monitor symptoms peak flow measurements drug usage and knowing how to deal with fluctuations in severity

of asthma according to written guidance.


A self- management plan would also include details of when to increase the dose of an inhaled steroid, when to take a short course of oral corticosteroids and when to use a nebulizer, how to monitor the effects of the nebulized dose and when to self-refer to a general practitioner or local hospital.


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