BRONCHIAL ASTHMA

1. BRONCHIAL ASTHMA

2. Definition: Asthma is a common chronic inflammatory condition of the lung airways whose cause is incompletely understood. Symptoms are cough, wheeze, chest tightness and shortness of breath, often worse at night. It has three characteristics: airflow limitation which is usually reversible spontaneously or with treatment airway hyper-responsiveness to a wide range of stimuli .

3. 3. Infiltration of the bronchi with eosinophils, T lymphocytes and mast cells with associated plasma exudation, oedema, marked smooth muscle hypertrophy, mucus plugging and epithelial damage. In chronic asthma, inflammation may be accompanied by irreversible airflow limitation.

4. Prevalence: In many countries the prevalence of asthma is increasing, particularly in the second decade of life where this disease affects 10-15% of the population. There is also a geographical variation, with asthma being common in more developed countries e.g.UK, but being much rarer in Far Eastern countries such as China, and in Africa and Central and Eastern Europe. Long-term follow-up in developing countries suggests that the disease may become more frequent as individuals become more 'westernized'.

5. Classification Asthma can be divided into: extrinsic - implying a definite external cause. occurs most frequently in atopic individuals who show positive skin-prick reactions to common inhalant allergens ,+ve family history of allergy, and usually high serum level of Ig E. Childhood asthma is often accompanied by eczema. late-onset asthma in adults is often due to sensitization to chemicals or biological products in the workplace, aspirin intolerance, or because they were given �-adrenoceptor-blocking agents for concurrent hypertension or angina.

6. Intrinsic asthma or cryptogenic - when no causative agent can be identified often starts in middle age ('late onset'). Family history of allergy is often - ve ,and the serum level of Ig E is not raised. Extrinsic causes must be considered in all cases of asthma and, where possible, avoided. Etiology: Asthma is a heterogeneous disease with interplay between genetic and environmental factors. Several risk factors have been implicated.

7. Endogenous Factors Genetic predisposition ,Atopy, Airway hyper-responsiveness, Ethnicity and Gender. Environmental Factors Occupational sensitizers, Indoor allergens, Outdoor allergens�, Passive smoking, Respiratory infections�. Triggers�� Allergens,�Upper respiratory tract viral infections,�Exercise and hyperventilation , Cold air,�Drugs ( blockers, aspirin)�,Stress�and Irritants (household sprays, paint fumes)�.

8. N.B: The term 'atopy' was used by clinicians at the beginning of the century to describe a group of disorders, including asthma and hay fever, that appeared: To run in families To have characteristic wealing skin reactions to common allergens in the environment To have circulating antibody in their serum that could be transferred to the skin of non-sensitized individuals. The term is best used to describe those individuals who readily develop antibodies of IgE class against common materials present in the environment. with many patients showing a family history of allergic diseases.

10. Pathology: The airway mucosa is infiltrated with activated eosinophils and T lymphocytes, and there is activation of mucosal mast cells. The degree of inflammation is poorly related to disease severity and may be found in atopic patients without asthma symptoms. Thickening of the basement membrane due to subepithelial collagen deposition; it is likely to be a marker of eosinophilic inflammation in the airway, as eosinophils release fibrogenic factors. The epithelium is often shed or friable, with reduced attachments to the airway wall and increased numbers of epithelial cells in the lumen. Metaplasia (stratified non ciliated) may occure.

11. Submucosa is oedematous and infiltrated with eosinophils , lymphocytes and mast cells with dilated capillaries. Muscles are hypertrophied. Mucus glands are enlarged.

13. Pathogenesis : The pathogenesis of asthma is complex and not fully understood. It involves a number of cells, mediators, nerves and vascular leakage that can be activated by several different mechanisms, of which exposure to allergens is among the most significant . The antigen is presented to T helper lymphocytes (THL) via the antigen presenting cells (macrophages) There are 2 subtypes of THL THL1?interleukin-2(IL-2)?re-stimulation of THL1 as well as stimulation of B lymphocytes?IgE secretion. THL2?IL-4,5,6?stimulation of B lymphocytes?IgE secretion.

14. Also THL2?IL-3? stimulation of mast cells to release mediators. IL-5,also stimulates oesinophils to release mediators. The antigen and IgE form a complex on mast cells and oesinophils stimulating them to release mediators. The released mediators ?airway smooth muscles contraction, mucusal oedema ,epithelial shedding, and inflammatory cells chemotaxis.

15. Clinical features : The principal symptoms of asthma are wheezing attacks and episodic shortness of breath. Symptoms are usually worst during the night. Cough is a frequent symptom that sometimes predominates and is often misdiagnosed as bronchitis. There is a wide range of variation in the frequency and duration of the attacks. Some patients have chronic symptoms. Clinical signs: May be normal(in between the attacks). Hyper inflation of chest , use of accessory muscles . Expiratory rhonchi Associated signs as nasal polyps, flexural eczema.

16. Investigations : There is no single satisfactory diagnostic test for all asthmatic patients. Respiratory function tests: Measurements of peak expiratory flow (PEF) on waking, prior to taking a bronchodilator and before bed after a bronchodilator, are particularly useful in demonstrating the variable airflow limitation that characterizes the disease. The diurnal variation in PEF is a good measure of asthma activity and is of help in the longer-term assessment of the patient's disease and its response to treatment. To assess possible occupational asthma, peak flows need to be measured for at least 2 weeks at work and 2 weeks off work.

17. Blood and sputum tests: Patients with asthma may have an increase in the number of eosinophils in peripheral blood (> 0.4 � 109/L). The presence of large numbers of eosinophils in the sputum is a more useful diagnostic tool. Chest X-ray: There are no diagnostic features of asthma on the chest X-ray, although over inflation is characteristic during an acute episode or in chronic severe disease. A chest X-ray may be helpful in excluding a pneumothorax, which can occur as a complication. Skin tests: Skin-prick tests should be performed in all cases of asthma to help identify allergic causes.

18. Management : Asthma is extremely common and causes considerable morbidity. The aims of treatment are to: Abolish symptoms Restore normal or best possible lung function Reduce the risk of severe attacks Enable normal growth to occur in children Minimize absence from school or employment.

19. This involves: patient and family education about asthma patient and family participation in treatment avoidance of identified causes where possible use of the lowest effective doses of convenient medications to minimize short-term and long-term side-effects. Control of extrinsic factors Measures must be taken to avoid causative allergens such as the house-dust mite, moulds and certain food stuffs (e.g eggs ,checolate), particularly in childhood. Active and passive smoking should be avoided, as should beta-blockers in either tablet or eye drop form. Individuals intolerant to aspirin may benefit by avoiding salicylates and should avoid NSAIDs.

20. 50% of individuals sensitized to occupational agents may be cured if they are kept permanently away from exposure. The remaining 50% continue to have symptoms that may be as severe as when exposed to materials at work, especially if they were symptomatic for a long time before the diagnosis was made. This emphasises: the importance of the rapid identification of extrinsic causes of asthma and their removal wherever possible (e.g. occupational agents, family pets) once extrinsic asthma is initiated, it may become self-perpetuating possibly by non-immune mechanisms.

21. Drug treatment : The mainstay of asthma therapy is the use of therapeutic agents delivered as aerosols or powders directly into the lungs The advantages of this method of administration are that drugs are delivered direct to the lung and the first-pass metabolism in the liver is avoided; thus lower doses are necessary and systemic unwanted effects are minimized. Both national and international guidelines have been published on the stepwise treatment of asthma based on three principles:

22. Asthma self-management with regular asthma monitoring using peak flow meters and individual treatment plans discussed with each patient and written down. The appreciation that asthma is an inflammatory disease and that anti-inflammatory (controller) therapy should be started even in mild cases. Use of short-acting inhaled bronchodilators (e.g. salbutamol and terbutaline) only to relieve breakthrough symptoms. Increased use of bronchodilator treatment to relieve increasing symptoms is an indication of deteriorating disease.

23. Drugs used in asthma Inhaled oral steroids short-acting relievers (salbutamol, terbutaline) Long-acting relief/disease controllers - Long-acting �2 agonists - salmeterol, formoterol - Sodium cromoglicate - Leukotriene modifiers Other agents with bronchodilator activity _ Antimuscarinic agents (ipratropium, oxitropium) _ Theophylline preparations

24. Steroid-sparing agents - Methotrexate - Ciclosporin - Gold - Intravenous immunoglobulin - Anti-IgE monoclonal antibody - Etanercept

25. The stepwise management of asthma

26. Acute severe asthma Patients with acute severe asthma typically have: inability to complete a sentence in one breath respiratory rate = 25 breaths per minute tachycardia = 110 beats/min (pulsus paradoxus, is not useful as it is only present in 45% of cases) PEF < 50% of predicted normal or best.

27. Features of life-threatening attacks are: a silent chest, cyanosis or feeble respiratory effort exhaustion, confusion or coma bradycardia or hypotension PEF < 30% of predicted normal or best (approximately 150 L/min in adults).

28. Treatment of severe asthma At home The patient is assessed. Tachycardia, a high respiratory rate and inability to speak in sentences indicate a severe attack. If the PEFR is less than 150 L/min (in adults), an ambulance should be called. (All doctors should carry peak flow meters.) Nebulized salbutamol 5 mg or terbutaline 10 mg is administered. Hydrocortisone sodium succinate 200 mg i.v. is given. Oxygen 40-60% is given if available. Prednisolone 60 mg is given orally.

29. At hospital The patient is reassessed. Oxygen 40-60% is given. The PEFR 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. Nebulized salbutamol 5 mg or terbutaline 10 mg is repeated and administered 4-hourly. Add nebulized ipratropium bromide 0.5 mg to nebulized salbutamol/terbutaline. Hydrocortisone 200 mg i.v. is given 4-hourly for 24 hours.

30. Prednisolone is continued at 60 mg orally daily for 2 weeks. Arterial blood gases are measured; if the Paco2 is greater than 7 kPa, ventilation should be considered. A chest X-ray is performed to exclude pneumothorax. One of the following intravenous infusions is given if no improvement is seen: salbutamol 3-20 �g/min, or terbutaline 1.5-5.0 �g/min, or magnesium sulphate 1.2-2 g over 20 min.

31. Arterial blood gases should always be measured in asthmatic patients requiring admission to hospital. Pulse oximetry is useful in monitoring oxygen saturation during the admission and reduces the need for repeated arterial puncture. Features suggesting very severe life-threatening attacks are: a high Paco2 > 6 kPa severe hypoxaemia Pao2 < 8 kPa despite treatment with oxygen a low and falling arterial pH.