Asthma is a chronic inflammatory disorder of the airways that cause recurrent episodes of wheezing,breathlessness,chest thightness and cough,particularly at night and in the early morning.Most of the asthma attacks are caused by sudden bronchospasms or bronchoconstriction triggered by medications,exercise,allergy,cigarette smokes and also wheather (cold ).
There are so many ways to categorized asthma.Typically asthma is categorized into intrinsic and extrinsic asthma.
Intrinsic asthma is an asthmatic attacks triggered by diverse,non-immune mechanisms,such as ingestion of aspirin,cold,exercise stress and inhaled irritant.
Extrinsin asthma is an asthma initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigens.
Asthma also can be categorized into mild intermittent,mild,moderate and severe depending on the frequency of asthma attacks and its severity of the clinical manifestations.
Another way to categorized asthma is based on its triggering factors that cause bronchospasm,such as,seasonal,exercise –induced,drug-induced,occupational asthma and asthmatic bronchitis in smokers.
Asthma is widely and differently distributed around the world.It is common mostly in children ( 35 % ) and less common in adults ( 10 % ).This showschildren are at greater risk of asthma than adults Asthma incidence is 1%/y in average. Severe asthma is reported by 1-3% of the general population (children and adults respectively).
Recent population show that the asthma prevalence increase observed worldwide in the past 30 years has now stopped in industrialised countries. Such phenomenon has been paralleled by an increase in the use of asthma medications.
However,there has been a significant increase of asthma in the Western world in the past three decades.
Clinicians have long known that asthma is not a single disease; it exists in many forms.
Evidence: Disease risks from early environmental factors and susceptibility genes, subsequent disease induction and progression from inflammation, and response to therapeutic agents.
What susceptibility genes are we talking about?
Studies suggest a genetic basis for airway hyperresponsiveness, including linkage to chromosomes 5q and 11q. Asthma clearly does not result from a single genetic abnormality; rather it is a complex multigenic disease with a strong environmental contribution. For example, allergic potential to inhaled allergens (e.g., dust mites, mold spores, cat dander) is found more commonly in asthmatic children or asthmatic adults whose asthma began in childhood than in those with adult-onset asthma.
Despite the explosion of information about asthma, the nature of its basic pathogenesis has not been established.
Histopathology: What do your sick cells look like due to asthma.
Edema, epithelial cell desquamation, and inflammatory cell infiltration are found not only in autopsy studies of severe asthma cases but even in patients with very mild asthma. Reconstructive lesions, including goblet cell hyperplasia, subepithelial fibrosis, smooth muscle cell hyperplasia, and myofibroblast hyperplasia can lead to remodeling of the airway wall. Although many types of descriptive studies have revealed a composite picture of asthma, they have failed to identify a basic unifying defect of neural mechanisms, inflammatory cells (mast cells, macrophages, eosinophils, neutrophils, and lymphocytes), mediators (interleukins, leukotrienes, prostaglandins, and platelet-activating factor), and intrinsic abnormalities of the arachidonic acid pathway and smooth muscle cells.
Immunology: How did the body help in the wrong way, aggravating asthmatic attacks?
1.The Th2 lymphocytes mediate allergic inflammation in atopic asthmatics by a cytokine profile that involves IL-4 (which directs B lymphocytes to synthesize IgE), IL-5 (which is essential for the maturation of eosinophils), and IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF).
2.Eosinophils are often present in the airways of asthmatics (more commonly in allergic but also in nonallergic patients), and these cells produce mediators that can exert damaging effects on the airways.
3.Anticytokine studies suggest that lipid mediators are products of arachidonic acid metabolism. They have been implicated in the airway inflammation of asthma and have been the target of pharmacologic antagonism by antileukotriene agents.
4.Prostaglandins are generated by the cyclooxygenation of arachidonic acid, and leukotrienes are generated by the lipoxygenation of arachidonic acid. The proinflammatory prostaglandins (prostaglandin [PG]D2, PGF2, and TXB2) cause bronchoconstriction, whereas other prostaglandins are considered protective and elicit bronchodilation (PGE2and PGI2, or prostacyclin).
5. Leukotrienes C4, D4, and E4compose the compound formerly known asslow-reacting substance of anaphylaxis,a potent stimulus of smooth muscle contraction and mucus secretion.
6.Ultimately, mediators lead to degranulation of effector or proinflammatory cells in the airways that release other mediators and oxidants, a common final pathway that leads to the chronic injury and inflammation noted in asthma.
The story during an asthmatic attack! The pathogenesis:
Inhaled allergens elicit TH2 response
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Favours IgE production and eosinophil recruitment
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Reexposure of allergens
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Stimulates degranulation of mast cells by antigen-induced-cross linking of IgE bound on mucosal cells
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Released of pre-formed mediators
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Bronchospasm, vasodilation, mucus production
↓ Late phase reaction
Inflammation with recruitment of neutrophils and eosinophils
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Eosinophils cause epithelial damage of the airways
Concept of Airway Remodeling: When asthma gets out of control!
The relation between the several types of airway inflammation (early-phase and late-phase events) and the concept of airway remodeling remain a source of intense research.
What is airway remodeling??
Persistent airflow obstruction despite aggressive anti-inflammatory therapies, including ICS and systemic corticosteroids.
Increases of smooth muscle mass
Mucous gland hyperplasia
Persistence of chronic inflammatory cellular infiltrates
Release of fibrogenic growth factors along with collagen deposition
Increased numbers and size of vessels in the airway (one of the most consistent features)
Coughing. Coughing from asthma is often worse at night or early in the morning, making it hard to sleep.
Wheezing. Wheezing is a whistling or squeaky sound that occurs when you breathe.
Chest tightness. This may feel like something is squeezing or sitting on your chest.
Shortness of breath. Some people who have asthma say they can't catch their breath or they feel out of breath. You may feel like you can't get air out of your lungs.
Chest pain
Signs that your asthma is probably getting worse include:
More frequent and bothersome asthma signs and symptoms
Increasing difficulty breathing (this can be measured by a peak flow meter, a simple device used to check how well your lungs are working)
An increasingly frequent need to use a quick-relief inhaler
The aims of treatment are to: 1) abolish symptoms 2) restore normal or best possible lung function 3) reduce the risk of severe attacks 4) enable normal growth to occur in children 5) minimize absence from school or employment.
This involves: 1) patient and family education about asthma 2) patient and family participation in treatment 3) avoidance of identified causes where possible 4) use of the lowest effective doses of convenient medications to minimize short-term and long-term side-effects.
General Types of Treatment
Drug Treatment - Is it administered as aerosols or powders directly into the lungs - Its advantages include direct delivery into the airways and first-pass metabolism in the liver is avoided; thus lower doses are necessary and systemic unwanted effects are minimized.
Drugs used in asthma :
1) Short acting relievers :
a) inhaled B2 agonists (salbutamol or terbutaline)
2) Long acting relieve / disease controllers : a) Inhaled long acting B2 agonists (salmeterol or formoterol) b) Inhaled corticosteroid (beclomethasone, budisemide and fluticasone) c) Compound inhaled salmeterol and fluticasone d) Sodium cromoglicate e) Leukoterine modifiers (montelukast, zafirlukast and zileuton)
3) Other agents with bronchodilator activity a) Inhaled antimuscaranic agents (ipratropium and oxitropium) b) Theophylline preparations c) Oral corticosteroids (prednisolone)
4) Steroid-sparing agents a) Methotrexate b) Cislosporin c) Intravenous immunoglobulins d) Anti-IgE monoclonal antibody (omalizumab)
Classification of drugs used in asthma :
B2-adrenoceptor agonists - most widely used bronchodilator preparations contain B2-adrenoceptor agonists that are selective for the respiratory tract and do not stimulate the B1 adrenoceptors of the myocardium. - relax the bronchial smooth muscle and is very effective in relieving symptoms but does little for the underlying inflammatory nature of the disease. - examples are Short-acting B-agonists (SABAs) such as salbutamol or terbutaline
Antimuscaranic bronchodilators - Muscarinic receptors are found in the respiratory tract; large airways contain mainly M3 receptors whereas the peripheral lung tissue contains M3 and M1 receptors - Nonselective muscarinic antagonists – ipratropium bromide (20– 40 μg three or four times daily) or oxitropium bromide (200 μg twice daily) – by aerosol inhalation can be useful during asthma exacerbations
Anti-inflammatory drugs - Sodium cromoglicate and nedocromil sodium prevent activation of many inflammatory cells, particularly mast cells, eosinophils and epithelial cells, but not lymphocytes, by blocking a specific chloride channel which in turn prevents calcium influx.
Inhaled corticosteroids - Patients who have regular persistent symptoms (even mild symptoms) need regular treatment with inhaled corticosteroids - Beclometasone dipropionate (BDP) is the most widely used inhaled steroid and other inhaled steroids include budesonide, fluticasone, mometasone and triamcinolone. - The unwanted effects of inhaled corticosteroids are oral candidiasis (5% of patients), and hoarseness due to the effect of corticosteroids on the laryngeal muscles. - Asthmatic patients who smoke are less responsive to inhaled corticosteroids, and additional therapy, e.g. with leukotriene receptor antagonists, is required.
Oral corticosteroids and steroid-sparing agents - Oral corticosteroids may be necessary for those individuals not controlled on inhaled corticosteroids and the dose should be kept as low as possible to minimize the side effects
Cysteinyl leukotriene receptor antagonists (LTRAs) - This class of drug targets one of the principal asthma mediators by inhibiting the cysteinyl LT1 receptor. - Montelukast, pranlukast (only available in South East Asia) and zafirlukast are given orally - LTRAs should be considered in any patient who is not controlled on low to medium doses of inhaled steroids - LTRAs are particularly useful in patients with aspirin-intolerant asthma, in those patients requiring high dose inhaled or oral corticosteroids and in asthmatic smokers. Because these drugs are orally active they are helpful in asthma combined with rhinitis and in young children with asthma and/or virus associated wheezing.
Monoclonal antibodies - It is a recombinant humanized monoclonal antibody that complexes with free IgE – omalizumab – blocking its interaction with mast cells and basophils.
Treatment for Severe Asthma
If patient is at home : 1) The patient is assessed. Tachycardia, a high respiratory rate and inability to speak in sentences indicate a severe attack. 2) If the peak expiratory flow rate is less than 150 L/min (in adults), an ambulance should be called. 3) Nebulized salbutamol 5 mg or terbutaline 10 mg is administered. 4) Hydrocortisone sodium succinate 200 mg i.v. is given. 5) Oxygen 40–60% is given if available. 6) Prednisolone 60 mg is given orally.
If patient is at hospital : 1) The patient is reassessed. 2) Oxygen 40–60% is given. 3) The peak expiratory flow rate is measured using a low-reading peak flow meter, as an ordinary meter measures only from 60 L/min upwards. Measure O2 saturation with a pulse oximeter. 4) Nebulized salbutamol 5 mg or terbutaline 10 mg is repeated and administered 4-hourly. 5) Add nebulized ipratropium bromide 0.5 mg to nebulized salbutamol/terbutaline. 6) Hydrocortisone 200 mg i.v. is given 4-hourly for 24 hours. 7) Prednisolone is continued at 60 mg orally daily for 2 weeks. 8) Arterial blood gases are measured; if the Paco2 is greater than 7 kPa, ventilation should be considered. 9) A chest X-ray is performed to exclude pneumothorax. 10) One of the following intravenous infusions is given if no improvement is seen: a) salbutamol 3–20 μg/min, or b) terbutaline 1.5–5.0 μg/min, or c) magnesium sulphate 1.2–2 g over 20 min.
Asthma is a disorder that recognizes no age group but it is more common in children. As it is a chronic disease, it may persist for decades. Generally, the prognosis of Asthma is quite good. The treatments available are excellent and control over this disease is easily achieved. However, asthma is the 3rd major cause of hospitalization in children under age of 15 in America. This condition can become very severe in children less than 5 years due to their narrow airways.
According to a study published in 2003, researchers followed patients with asthma for more than 30 years. About a third of the patients had outgrown the condition and became symptom free in that particular study. In general, we can say that the more severe the childhood asthma, the higher the chances that it will persist into adulthood. There is also evidence that asthma can cause damage and lead to permanent fibrosis in some patients. The risk for injury is highest, however, when asthma strikes children aged 3 to 5 years.
For children who develop asthma between ages 6 to 12, there does not seem to be any significant risk of long term lung damage. Children are able to adapt well to living with asthma and even children with severe asthma are able to function optimally in all areas of life.
In adults, the long term outlook of asthma patients depends on the severity:
In mild to moderate cases, asthma can improve over time and many become symptom free
In some severe cases, adults may experience improvement depending on the degree of obstruction and effectiveness of treatment
In about 10% of severe persistent cases, changes in airway structure lead to irreversible and progressive disorders of the lung, even in patients that are treated aggressively
Lung function declines faster in asthmatic patients compared to those who are well. The decline in lung function is aggravated in those who smoke and in those with excessive mucus production (poor treatment control)
Death from asthma is relatively uncommon and most are preventable. Even when it is not life threatening, asthma can be debilitating and frightening. Asthma that is not properly controlled can interfere with daily activities.
Follow your asthma action plan in which you can write adetailed plan for taking medications and managing an asthma attack with your doctor and health care team. Then be sure to follow your plan. Asthma is an ongoing condition that needs regular monitoring and treatment. Taking control of your treatment can make you feel more in control of your life in general.
If your asthma attacks are triggered by an allergic reaction, avoid your triggers as much as possible-ranging from pollen and mold to cold air and air pollution that can trigger asthma attacks.
Keep taking your asthma medications as prescribed after you are discharged. This is extremely important. Although the symptoms of an acute asthma attack go away after appropriate treatment, asthma itself never goes away.
Periodic assessments and ongoing monitoring of asthma are essential to determine if therapy is adequate. Patients need to understand how to use a peak flow meter and understand the symptoms and signs of an asthma exacerbation.
Regular follow-up visits (at least every six months) are important to maintain asthma control and to reassess medication requirements.
Patients with persistent asthma should be given an annual influenza vaccine.
