Asthma : types, pathophysiology, diagnosis and treatment

 Bronchial asthma

Asthma is a chronic inflammatory disease of the smaller airways, characterised by episodic, reversible bronchial obstruction due to hyper-responsiveness of tracheobronchial tree to a multiplicity of intrinsic and extrinsic stimuli manifested clinically by paroxysms of polyphonic wheeze, dyspnoea, chest tightness and cough which may be relieved spontaneously or as a result of therapy.

ASTHMA BRONCHIOLE

Types of Asthma

Extrinsic Asthma (Atopic Asthma, Early Onset Asthma)

Onset is in childhood. It occurs in atopic individuals who readily form IgE antibodies in response to allergens. Atopic patients can be identified by skin sensitivity tests.

Intrinsic Asthma (Non-atopic Asthma, Late Onset Asthma)

It can be begin at any age, especially in late adulthood. There is no role for allergens in the production of disease.

Nocturnal Asthma

It is defined as an overnight fall of more than 20% in the FEV1 or PEFR. This is presumed to be due to:

• Early morning fall in circulating adrenaline.
• Overnight changes in vagal tone (increased vagal tone in early morning).
• Airway cooling at night.
• Circadian changes in plasma cortisol concentration (midnight to early morning fall in cortisol level).

Gastric Asthma

Worsening of asthma after meals or dyspnoea occuring only after meals is due to gastro-oesophageal reflux. This can be treated by avoiding oral bronchodilators and instituiting anti-reflex therapy.

Exercise-induced Asthma

Asthma is induced by exercise and inhaled bronchodilators or sodium cromoglycate should be given before exercise.

Episodic Asthma

Patients has no respiratory symptoms between episodes of asthma.

Chronic Asthma

Symptoms may be chronic unless controlled by appropriate therapy. It may simulate chronic bronchitis.

Corticosteroid Resistance Asthma

Bronchial asthma fails to respond to a high dose of oral prednisolone-40 mg once daily over two weeks.

Brittle Asthma

Bronchial asthma in which there is choatic variations in lung functions despite appropriate therapy.

Type 1: They manifest with persistant pattern of variability and require oral corticosteroids or beta 2 agonist infusion.

Type 2: They have normal or near normal lung function, but occurs unpredictable fall in lung function and sudden death.

Factors Precipitating Asthma

• Cold air.
• Tobacco smoke.
• Dust, acrid fumes.
• Emotional stress.
• Respiratory infections (viral, bacterial)
• Exercise.
• Drugs- NSAIDs especially aspirin, Beta-blockers.
• Chemicals- Sulfiting agents like Na or K bisulfite, sulphur dioxide, etc.
• Allergens- 1. Ingested (fish, nuts, strawberries), 2. Inhaled (dust, pollen, house dust mite), 3. Food additives (tartrazine, metabisulfite preservative, monosodium glutamate or ajinomoto), 4. Occupational allergens (grain-dust, wood dust)

Bronchial Asthma Pathophysiology 

Chronic airway inflammation as evidenced by cellular infiltration of airway by activated eosinophils, mast cells, macrophages and T-lymphocytes.

Released mediators from the above cells cause bronchial smooth muscle contraction.

Denudation and desquamation of the epithelium forming mucous plugs that obstruct the airway.

Airway remodelling as evidenced by:

• Smooth muscle hypertrophy and hyperplasia.
• Goblet cell and sub-mucosal gland hypertrophy leading to mucous hypersecretion.
• Collagen deposition causing thickening of lamina reticularis.
• Cellular infiltration, oedema and possible airway wall thickening.

Clinical features of Bronchial Asthma

• Widespread, polyphonic, high pitched wheezes are heard.
• Typical symptoms are recurrent episodes of wheezing, chest tightness, breathlessness and cough.
• Expiratory wheeze is heard with mild bronchoconstriction.
• Inspiratory and expiratory wheezes are heard in moderate bronchoconstriction.
• Inspiratory wheeze is heard in severe bronchoconstriction.
• In near fatal asthma, the chest is silent.

Bronchial Asthma Diagnosis (Investigations)

1. Chest X-ray

Chest X-ray should be taken to rule out other causes of wheezing and also to rule out presence of pneumothorax in all case of severe acute asthma.

2. Pulmonary Function Test (PFT)

PFT shows obstructive type of lung disease. FEV1 following 2 puffs of beta agonist shows an increase by 15% or greater than the previous level.

3. Peak Expiratory Flow (PEF)

Serial recordings of PEF may show overnight fall (morning dip) and subsequently rise during the day in patients with asthma.

There are increased eosinophils in sputum and blood. Serum IgE is elevated in atopic asthma.

4. Exhaled Nitric Oxide

• Non-invasive test to measure eosinophilic airway inflammation.
• Elevated levels are reduced by inhaled corticosteroids.
• Test of compliance with therapy.

Treatment of Bronchial asthma (Management)

The stepwise approach to the management of asthma

Step 1: Occasional use of inhaled short-acting Beta2-adrenoreceptor agonist bronchodilators

For patients with mild intermittent asthma (symptoms less than once a week for 3 months and fewer than 2 nocturnal episodes per month), it is usually sufficient to prescribed an inhaled short-acting Beta2-agonist, such as salbutamol or terbutaline.

Metered-dose inhaler remains the most widely prescribed.

Step 2: Introduction of regular preventer therapy

Regular anti-inflammatory therapy (preferably inhaled corticosteroids (ICS), such as beclomethasone, budesonide (BUD), fluticasone or ciclesonide) should be started in addition to inhaled Beta2-agonists taken on as required basis for any patient who:

• has experienced an exacerbation of asthma in the last 2 years.
• uses inhaled beta2-agonists 3 times a week or more.
• is awakened by asthma one night per week.

For adults, a reasonable starting dose is 400 microgram beclometasone dipropionate (BDP), although higher doses may be required in smokers.

Alternative but much less effective preventive agents include chromones, leukotriene receptor antagonists, and theophyllines.

Step 3: Add-on therapy

If a patient remains poorly controlled despite regular use of an inhaled glucocorticoid, a further increase in the dose of inhaled glucocorticoid may benefit some patients, but in general, add-on therapy should be considered in adults taking 800 microgram/ day BDP (or equivalent).

The addition of a long-acting beta2-agonist (LABA) to an inhaled glucocorticoid provides more effective asthma control. A fixed combination of budesonide and formoterol may be used as both rescue and maintenance therapy.

Oral leukotriene receptor antagonists (montelukast 10mg daily) may facilitate a reduction in the dose of inhaled glucocorticoid and control exacerbations.

Step 4: Poor control on moderate dose of inhaled glucocorticoid and add-on therapy: addition of a fourth drug

In adults, the dose of inhaled glucocorticoid may be increased to 2000 microgram BDP/ BUD (or equivalent) daily.

Leukotreine receptor antagonists, long-acting antimuscarinic agents, theophyllines or a slow-release beta2-agonist may be considered.

Step 5: Continuous or frequent use of oral glucocorticoids

At this stage, prednisolone therapy should be prescribed in the lowest amount necessary to control symptoms.

Patients who are on long-term glucocorticoid tablets (>3 months) may develop osteoporosis, bisphosphonates may be considered.

In patients who continue to experience symptoms and shows impaired lung function despite step 5 therapy, omalizumab, a monoclonal antibody directed against IgE, should be considered for those with a prominent atopic phenotype.

Mepolizumab, a monoclonal antibody that blocks the binding of IL-5 to its receptor on eosinophils, should be considered in those with eosinophilic-mediated disease.

Step-down therapy

Once asthma control is established, the dose of inhaled or oral glucocorticoid should be titrated to the lowest dose.

Decreasing the dose of glucocorticoid by around 25-50% every 3 months is a reasonable therapy for most patients.