BRONCHIAL ASTHMACLASSIFICATION,CLINICAL FEATURES AND MANAGEMENT

                                              BRONCHIAL ASTHMA.

DEFINITION:

Paroxysmal wheeze and breathlessness occurring on account of narrowing of airways.

In essence –hyper reactive airways- where in inflammatory reaction involves all the 3 layers producing

1.       bronchial  smooth muscle spasm

2.       Mucosal swelling

3.       Viscous bronchial secretions

All 3 factors thus causing narrowing of airway.

Note:

Asthma is a reversible condition (COPDand Chronic bronchitis-irreversible)

 Asthma affects bronchi mainly(emphasyma-alveoli)

CLASSIFICATION: 

According to severity,etiology,according to type of airflow obstruction                                                                                                                                                                                               

As per severity:

Intermittent             less than once a week

Mild persistent                    .once per week/less than once per day

Moderately persistent         daily

Severe persistent                  daily

·         A spectrum of severity is presented in asthma rather than a discrete severity group.

·         If grading is difficult consider the most likely group   and start treatment appropriate for that,

-monitor by PEF and reassess. 

·         Also severity can vary with time.

CLINICAL FEATURES: 

Narrowing of airways causes the classic symptoms wheeze, cough, breathlessness

Cough is especially nocturnal and dry

 Attacks can be episodic or chronic (overlap can occur)                                                                                                  

 Generally episodic in atopic individuals –

 In non atopic-chronic asthma

  

Asthmatic attacks can manifest in 2 clinical forms severity wise.

·         Acute asthmatic exacerbation

·         Steady chronic  asthma

 In Steady state:

Asthma starts episodically initially, becomes continuous later, with

-symptoms of nocturnal cough, exertional  dyspnoea ,tightness in the chest

-can steadily worsen and lead to acute exacerbation

Acute severe asthma: features

Dyspnea even at rest

Patient confused/drowsy/agitated

cyanosed

Accessory muscles of respiration functioning

Respiratory rate.>30per min

Pulse rate.160/min

Inability to talk full sentences

PaO₂ less than 60%; PaCO more than45%

Age group

Childhood asthma

Adult onset asthma

But can start at any age, in different situations

Clinical variants of Asthma (Following have to be looked into for optimal management)                                                                          

·         Cough variant asthma

Cough is the sole manifestation

Persistent cough-specially manifest in children

For Relief-Anti asthmatics after investigations

·         Nocturnal asthma

Definition criteria-

Overnight fall in FEV1 by >20%or of Peek Expiratory flow rate( PEFR )

       Causes of nocturnal nature

( Air way sensitivity at night increases  8 fold, Airway cooling at night, Plasma concentration of cortisol and adrenalin fall at  early morning. GERD reflux and aspiration)

·         Gastric asthma

Gastro esophageal reflux worsens asthma after meals /

Symptoms occurring only after meal suggest GERD

·         Aspirin sensitive asthma

Asthma, nasal polyp and aspirin sensitivity constitute “Samptars triad”

As a general rule avoids aspirin and NSAIDs in asthma; paracetamol may be used.

·         Exercise induced Asthma

This feature can be sole manifestation –treat with bronchodilators Short acting β2 agonists

               And with sodium Cromoglycate- before exercise

Triggers”  (allergens)which worsen the symptoms are-   

Exercise, cold, chemicals pollen, air pollution, animal dandruff, viral infections,strong emotions

 These triggers cause bronchial hypersensitivity through vagal nerve and Beta adrenergic receptors

-in the airways. 

Certain existing diseases can worsen asthma and are to be looked for:

  Sinusitis, Thyrotoxicosis,

Hypertension (antihypertensive like beta blockers and ACE inhibitors worsen asthma)                                                                                   

                               

HISTORY, CLINICAL PICTURE

Presence of following warrant the diagnosis of asthma:

·         History:

·         H/o atopy

I.e. h/o allergic rhinitis, atopic dermatitis, eczema, or utricaria

·         Wheeze and dyspnoea which are episodic and become continuous later.

·         Unexplained cough; viscid sputum may accompany.

·         Past h/o eosinophilia, asthmatic bronchitis, or allergic bronchitis

DIAGNOSIS

Diagnosis is essentially clinical

·         -Chronic recurrent or persistent wheeze which responds to bronchodilators

·         Cough may or may not be present(except in cough variant asthma)

·         Supporting Features in diagnosis;

·         Family h/o atopy, asthma

·         Nocturnal cough or  wheeze, exercise induced wheeze

·         Seasonal variation in symptoms

Cough alone is a poor marker of asthma except in cough variant asthma where cough alone is a symptom

Additional diagnostic supports

Demonstrating reversible airway obstruction by measuring PEFR or FEV1

After β₂ agonist administration, PEF increases by 20% in 10 minutes.

 If the diagnosis is uncertain- broncho provocative tests is done; but should be performed only by specialist.

DIFFERENTIAL DIAGNOSIS

ACUTE SEVERE ASTHMA (Status Asthmaticus is an obsolete term)

·         Symptoms

Too breathless to speak (unable to speak complete sentences)

·         SIGNS
Pallor, sweating, exhaustion,  disorientation/unconsciousness

Cyanosis, tachycardia, pulse rate.110/min, bradycardia warrants immediate resuscitation

Tachypnea. Respiratory rate >25/min;

Accessory muscles of respiration working

Pulsus paradoxus

Silent chest indicates severe airway obstruction; little air moving in and out of lung to generate rhonchi.

PEFR<40 200l="" absolute="" min="" of="" or="" p="" predicted="" value="">

Arterial blood gas-PO₂ falls  PCO2 rises ( after initial fall due to hyperventilation0

·         INVESTIGATIONS

1.       Normal chest x-ray/increased vascular markings

2.       Peripheral smear showing eosinophilia

3.       Spirometry showing Low FEV₁/FVC ratio

FEV₁-The amount of air forcibly expired in the first second of an FVC manoeuvre.

FVC-the maximum amount of air forcibly expired after maximum expiration

A ratio of FEV1/FVC of less than 80% indicates airflow obstruction.

Also if after bronchodilators the absolute value of FEV₁ increases by more than20%,it indicates reversible airflow obstruction.

4.       Peak Expiratory Flow Rate:(PEFR)

5.       PEFR is a measure of the maximum expiratory flow rate during a forced expiration.

A miniature peak flow meter simple ,portable and cheap hand held device is used.

Advantage; patient may be monitored at home avoiding hospitalization. In moderate asthma.

Normal PEFR are600-800ltrs/min. for males and 400-600ltrs /min for females.

6.       EXERCISE TEST;

After an exercise challenge, PEFR or FEV₁ falls by more than 20%.

7.       Allergy test:many with asthma have positive allergy test;but it may not be the cause of symptoms.

Further investigations for in -patient

8.       Electrolytes-hyperkalemia can occur due to β2 agonist, steroid or diuretic therapy.

9.       E.C.G-To evaluate myocardial ischemia.

10.   10.Arterial Blood Gas –in severe cases

AIM OF TREATMENT:

1.       Relieving symptoms

2.       Controlling airway inflammation so that no attacks occur

 ESSENTIAL FACTORS IN MANAGEMENT OF BRONCHIAL ASTHMA

1.       Assessment of severity of asthma (refers to patient symptoms between acute attacks)

2.       drug therapy

For symptom relief

 For symptom prevention

3.       Environmental management-by avoiding allergens and respiratory irritants

4.       Prevention of the following

Prevention and treatment of acute exacerbations

Prevention of irreversible airway changes

Mortality

5.       Maintenance of the following

As far as possible maintain Lung functions normal

Maintain activity levels at normal state

(attend work regularly,restful sleep/normal growth in children)

6.       Avoid adverse effects of drug (optimal use of medication)

7.       Follow up -and regular reevaluation for chronic cases

8.       Patient education

CLASSIFICATION OF SEVERITY OF ASTHMA

CATEGORY	DAY TIME SYMPTOMS	NIGHT TIME SYMPTOMS	PEF( predicted)	Variability of PEFRorFEV1
INTERMITTENT	≤ 2/week≤	≤1per month	≥80%	<20 p="">
MILD	2-4 per week	2-4 per month	≥80%	20-30%
MODERATE	>4perweek	>4 per month	60-80%	>30%
SEVERE	Continuous	Frequent	<60 p="">	>30%

START TREATMENT AT ANY STEP DEPENDING UPON THE LEVEL OF SEVERITY

 Treatment of acute severe asthma

Initial assessment

Immediate:

Ability to speak

Vital signs

Measurement of PEF unless patient is too ill to perform PEF

Arterial blood gas analysis

TREATMENT of Acute severe Asthma

1.Oxygen

High humidified Oxygen concentration 

Goal  Sao2 >92%

If appropriate oxygenation is not arrived   assisted ventilation

2. Inhaled brocho dilators-in high dose

Short acting β₂Agonist  Salbutamol   (5mg/hr)

Via nebulizer  or via metered dose inhaler through a space devisor

3. Inhaled anticholinergics

(Iptratropium  bromide may be added )

4.Systemic corticosteroids

IV hydrcotisone200mg-if patient unable to swallow or is vomiting

Intravenous fluids

Subsequent management

IV fluids

To treat dehydration and acidosis

Normal saline+sodium bicarbonate/lactate infusion

If salbutamol induced hypokalemia is present –potassium supplements

If patient fails to improve

IV magnesium sulphate

IV Beta2 agonists

IV aminophylline

IV leukotriene receptor antagonists

Anesthetics

Mechanical ventilation

Indication

Coma

Respiratory arrest

Deteoration of ABG inspite of optimal therapy

Exhaustion,confusion,drowsiness

Monitoring of treatment

Record PEF every 15-30 min

Serum concentration of aminophyline monitoring (if used)

Rpt ABG-

If initial PaCO₂ was raised

PaO₂ was low or If patient deteriorates.

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PHARMACOTHERAPHY

 POINTS OF CLINICAL IMPORTANCE

Principles involved:

1.       Since asthma is a inflammatory disease regular anti-inflammatory drugs are indicated.

2.       Inhaled therapy is preferable

Inhaled β₂ agonist is cheaper than syrup/tablets

3.       I n occasional attacks use inhalers on an as-needed basis

4.       In moderate-severe cases use anti-inflammatory drugs :inhaled steroids ,then inhaled broncho dilators

5.       Acute severe asthma needs intensive care therapy

TWO BASIC CATEGORIES OF MEDICINES FOR ASTHMA

1. RELIEVERS-              Relieve acute symptoms

2. PREVENTERS- prevent further attacks -anti-inflammatory

Point of clinical importance:

In mild asthma – use relievers as needed

In persistent asthma-control medicines are  taken on regular basis which prevent attacks.

1.  RELIEVERS-QUICK RELIEF MEDICATIONS which relieve the symptoms first

 Mainly broncho Dilators and Anticholinergics

Used to relieve the symptoms by broncho dilatation-act by relaxing smooth musclesof bronchi.

A.      β₂ agonist-Short acting)-

usually self administered in inhalant form

(if patient is unable to use inhalant oral treatment is given)

β₂ agonist provide temporary relief only-do nothing to  solve the underlying problem

    B. Anticholinergics.(Ipratropium bromide)

Mode of action-inhibit vagally mediated broncho constriction

Less powerful than β₂ agonist and slower in action-

 takes 30-60 minutes for good effect

Can be used as substitute for β2 agonist (if intolerant) or as additive

Not proved useful for long term use.

C.Methyl     Xanthines   (e.g.theophylline,aminophylline)

Usable in combination with inhaled steroids SR theophylline –can control nocturnal asthma

Usable as an alternative to ICS in some cases of mild persistent asthma-(ifICs not available or if oral therapy is desired by the patient);

but less effective 

have less favorable side effects profile.

Used only occasionally these days.

2.PREVENTERS

(LONG TERM CONTROL MEDICATION)

               Used on regular basis to prevent the attack, not for treatment during the attack

Prevent patient going for chronic asthma

               Preventers are anti inflammatory drugs.

Mode of action:

 The airway inflammation -the hall mark of asthma, is modified by these drugs

In asthma bronchi are not only constricted but are also inflamed ‘hyper reactive,

Irritable at slightest provocation-which is to be controlled by anti inflammatory drugs

Administration:

Preventers are used twice a day -whether or not symptoms are present

Used in all patients with persistent asthma

drugs in this group-

·         Frequently used drugs

anti-inflammatory drugs corticosteroids .( Inhaled,oral or IV)

  broncho dilators

·         other anti-inflammatory drugs

Leukotriene antagonists

Mast cell stabilizers    

                                                                                                                            

2.1.INHALED CORTICOSTEROIDS (ICS)

ICS are the most effective drug for asthma

Anti inflammatory in action

- reduce the frequency of acute attacks and thus improve the quality of life

Early use of ICS prevents fixed airway obstruction occurring later.

 improve lung functions,

Also relieve the symptoms in addition to preventive action

Indications 

ICS is first line drug for moderate and severe Persistent asthma

In mild form indication is controversial

Dose
                         optimal dose-is lowest dose needed for good disease control

         Dose must be individualized and titrated

        Increasing the dose may not be effective always

        High dose of inhaled steroids may cause systemic effects

        Efficacy of ICS is improved by  using spacer devices

        Dry powder devices like tubohaler /accuhaler increase the drug delivery to lungs

        -therefore low doses are advised in such devices

         Usually administered twice daily

         Names of steroids:

         Prednisolone, hydrocortisone betamethasone, , beclomethasone, budesonide,  

         triamcinalone,  -fluticasone

         Although the different products of ICS vary in milligram potency, for practical purposes,    

        doses are measured in puffs on the inhaler.

2.2.BRONCHO DILATORS-see above

2.3.LEUKOTRIENE BLOCKERS (RECEPTOR ANTAGONISTS   )

  Mode of action- These inhibit the effects of leukotrienes –products of arachidonic acid 

  metabolism

Onset of action is rapid (within 1-3 hrs)

Indications-

Indicated in persistent asthma of all degrees.

Attenuate exercise induced asthma

Are of value in aspirin induced asthma.

May act as steroid sparing agent

Use as monotherapy in mild persistent asthma debated

               Disadvantage –Churg-Strauss , a systemic vasculitis is reported

        Common side effect-headache,Gi disturbance

Name-Monteleukast –10mg HS (5mg chewable tabs for children)(SINGULAIR)

       Zafirleukast  -20mgBID (ACCOLATE)

2.4.MAST CELL STABILISERS          (CROMONES)

These are Mast cell stabilizers-prevent release of inflammatory mediators from cell granules

Sodium Cromoglycate and Nedocromil, Ketotifen

Have weak anti inflammatory effects

Useful in atopics with mild asthma

Disadvantages; high cost, requires frequent dosing, poor efficacy

Main advantage is good safety profile.

 Useful In asthmatics with persistent cough if optimal dose of ICS is ineffective

Useful for the prevention of exercise induced asthma

      

2.5.OTHER DRUGS

·         Oral Corticosteroids

Indicated in poorly controlled severe asthma

Short course of oral steroids are usually necessary in acute exacerbations

(Predinisolone1-2mg/kg/day with upper limit of 60mg /day)

Dis advantage-long term use cause systemic effects

Need for maintenance therapy if no control with high dose Inhaled steroids

Frequency-daily or alternate day steroids

in children take extra care in stress ful situation like surgery.

·         ANTI IGEN  ANTIBODY

Omilizumab which block the immune system pathway triggered by allergens

·         Long term β₂ agonist(LABA )inhalers open the airways for several hours

        Salmeterol, formoterol administered twice daily since they are long acting

       nocturnal symptoms are controlled by this sustained action

       Prevent exercise induced asthma (provide longer protection than short acting)

       Formoterol may be useful in acute asthma because of quick onset of action in 15 min.

        LABA inhalers have synergistic effect with ICS (better effect than doubling dose of steroids)

       Side effects-palpitations tremors

Note: Single medication that  combines steroids and bronchodilators  may be used.

·         Anti histamines

-          Have shown no proven benefit;

PATHOPHYSIOLOGY OF ASTHMA

PAthophysiology of asthma  is a very complex and controversial one.

Pathophysiology forms the basis of therapeutics of asthma

 Two basic entities that occur :

1. ROAD-Reversible Airway Obstruction

2.  BHR-Bronchial Hyper reactivity.

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