Cause Asthma runs in families, so that parents with asthma have a strong risk of having children with asthma, or with other atopic (see ATOPY) illnesses such as HAY FEVER or eczema (see DERMATITIS). There is therefore a great deal of interest in the genetic basis of the condition. Several GENES seem to be associated with the condition of atopy, in which subjects have a predisposition to form ANTIBODIES of the IgE class against allergens (see ALLERGEN) they encounter – especially inhaled allergens.
The allergic response in the lining of the airway leads to an in?ammatory reaction. Many cells are involved in this in?ammatory process, including lymphocytes, eosinophils, neutrophils and mast cells. The cells are attracted and controlled by a complex system of in?ammatory mediators. The in?amed airway-wall produced in this process is then sensitive to further allergic stimuli or to non-speci?c challenges such as dust, smoke or drying from the increased respiration during exercise. Recognition of this in?ammation has concentrated attention on anti-in?ammatory aspects of treatment.
Continued in?ammation with poor control of asthma can result in permanent damage to the airway-wall such that reversibility is reduced and airway-narrowing becomes permanent. Appropriate anti-in?ammatory therapy may help to prevent this damage.
Many allergens can be important triggers of asthma. House-dust mite, grass pollen and animal dander are the commonest problems. Occupational factors such as grain dusts, hard-metals fumes and chemicals in the plastic and paint industry are important in some adults. Viral infections are another common trigger, especially in young children.
The prevalence of asthma appears to be on the increase in most countries. Several factors have been linked to this increase; most important may be the vulnerability of the immature immune system (see IMMUNITY) in infants. High exposure to allergens such as house-dust mite early in life may prime the immune system, while reduced exposure to common viral infections may delay the maturation of the immune system. In addition, maternal smoking in pregnancy and infancy increases the risk.
Clinical course The major symptoms of asthma are breathlessness and cough. Occasionally cough may be the only symptom, especially in children, where night-time cough may be mistaken for recurrent infection and treated inappropriately with antibiotics.
The onset of asthma is usually in childhood, but it may begin at any age. In childhood, boys are affected more often than girls but by adulthood the sex incidence is equal. Children who have mild asthma are more likely to grow out of the condition as they go through their teenaged years, although symptoms may recur later.
The degree of airway-narrowing, and its change with time and treatment, can be monitored by measuring the peak expiratory ?ow with a simple monitor at home – a peak-?ow meter. The typical pattern shows the peak ?ow to be lowest in the early morning and this ‘morning dipping’ is often associated with disturbance of sleep.
Acute exacerbations of asthma may be provoked by infections or allergic stimuli. If they do not respond quickly and fully to medication, expert help should be sought urgently since oxygen and higher doses of drugs will be necessary to control the attack. In a severe attack the breathing rate and the pulse rate rise and the chest sounds wheezy. The peak-?ow rate of air into the lungs falls. Patients may be unable to talk in full sentences without catching their breath, and the reduced oxygen in the blood in very severe attacks may produce the blue colour of CYANOSIS in the lips and tongue. Such acute attacks can be very frightening for the patient and family.
Some cases of chronic asthma are included in the internationally agreed description CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) – a chronic, slowly progressive disorder characterised by obstruction of the air?ow persisting over several months.
Treatment The ?rst important consideration in the treatment of asthma is avoidance of precipitating factors. When this is a speci?c animal or occupational exposure, this may be possible; it is however more di?cult for house-dust mite or pollens. Exercise-induced asthma should be treated adequately rather than avoiding exercise.
Desensitisation injections using small quantities of speci?c allergens are used widely in some countries, but rarely in the UK as they are considered to have limited value since most asthma is precipitated by many stimuli and controlled adequately with simple treatment.
There are two groups of main drugs for the treatment of asthma. The ?rst are the bronchodilators which relax the smooth muscle in the wall of the airways, increase their diameter and relieve breathlessness. The most useful agents are the beta adrenergic agonists (see ADRENERGIC RECEPTORS) such as salbutamol and terbutaline. They are best given by inhalation into the airways since this reduces the general side-effects from oral use. These drugs are usually given to reverse airway-narrowing or to prevent its onset on exercise. However, longer-acting inhaled beta agonists such as salmeterol and formoterol or the theophyllines given in tablet form can be used regularly as prevention. The beta agonists can cause TREMOR and PALPITATION in some patients.
The second group of drugs are the antiin?ammatory agents that act to reduce in?ammation of the airway. The main agents in this group are the CORTICOSTEROIDS. They must be taken regularly, even when symptoms are absent. Given by inhalation they have few side-effects. In acute attacks, short courses of oral steroids are used; in very severe disease regular oral steroids may be needed. Other drugs have a role in suppressing in?ammation: sodium cromoglycate has been available for some years and is generally less e?ective than inhaled steroids. Newer agents directed at speci?c steps in the in?ammatory pathway, such as leukotriene receptor-antagonists, are alternative agents.
Treatment guidelines have been produced by various national and international bodies, such as the British Thoracic Society. Most have set out treatment in steps according to severity, with objectives for asthma control based on symptoms and peak ?ow. Patients should have a management plan that sets out their regular treatment and their appropriate response to changes in their condition.
Advice and support for research into asthma is provided by the National Asthma Campaign.
See www.brit-thoracic.org.uk
Prognosis Asthma is diagnosed in 15–20 per cent of all pre-school children in the developed world. Yet by the age of 15 it is estimated that fewer than 5 per cent still have symptoms. A study in 2003 reported on a follow-up of persons born in 1972–3 who developed asthma and still had problems at the age of nine. By the time these persons were aged 26, 27 per cent were still having problems; around half of that number had never been free from the illness and the other half had apparently lost it for a few years but it had returned.... asthma
Granulocytes Also known as polymorphonuclear leucocytes (‘polys’), these normally constitute 70 per cent of the white blood cells. They are divided into three groups according to the staining reactions of these granules: neutrophils, which stain with neutral dyes and constitute 65–70 per cent of all the white blood cells; eosinophils, which stain with acid dyes (e.g. eosin) and constitute 3–4 per cent of the total white blood cells; and basophils, which stain with basic dyes (e.g. methylene blue) and constitute about 0·5 per cent of the total white blood cells.
Lymphocytes constitute 25–30 per cent of the white blood cells. They have a clear, non-granular cytoplasm and a relatively large nucleus which is only slightly indented. They are divided into two groups: small lymphocytes, which are slightly larger than erythrocytes (about 8 micrometres in diameter); and large lymphocytes, which are about 12 micrometres in diameter.
Monocytes Motile phagocytic cells that circulate in the blood and migrate into the tissues, where they develop into various forms of MACROPHAGE such as tissue macrophages and KUPFFER CELLS.
Site of origin The granulocytes are formed in the red BONE MARROW. The lymphocytes are formed predominantly in LYMPHOID TISSUE. There is some controversy as to the site of origin of monocytes: some say they arise from lymphocytes, whilst others contend that they are derived from histiocytes – i.e. the RETICULO-ENDOTHELIAL SYSTEM.
Function The leucocytes constitute one of the most important of the defence mechanisms against infection. This applies particularly to the neutrophil leucocytes (see LEUCOCYTOSIS). (See also ABSCESS; BLOOD – Composition; INFLAMMATION; PHAGOCYTOSIS; WOUNDS.)... leucocytes
Red blood cells (also known as RBCs, red blood corpuscles, or erythrocytes) transport oxygen from the lungs to the tissues (see respiration). Each is packed with haemoglobin, enzymes, minerals, and sugars. Abnormalities can occur in the rate at which RBCs are either produced or destroyed, in their numbers, and in their shape, size, and haemoglobin content, causing forms of
anaemia and polycythaemia (see blood, disorders of).
White blood cells (also called WBCs, white blood corpuscles, or leukocytes) protect the body against infection and fight infection when it occurs. The 3 main types of are granulocytes (also called polymorphonuclear leukocytes), monocytes, and lymphocytes. Granulocytes are further classified as neutrophils, eosinophils, or basophils, and each type of granulocyte has a role in either fighting infection or in inflammatory or allergic reactions. Monocytes and lymphocytes also play an important part in the immune system. Lymphocytes are usually formed in the lymph nodes. One type, a T-lymphocyte, is responsible for the delayed hypersensitivity reactions
White (see allergy) and Red blood blood cell is also involved in cell (neutrophil) protection against cancer. T-lymphocytes manufacture chemicals, known as lymphokines, which affect the function of other cells. In addition, the T-cells moderate the activity of B-lymphocytes, which form the antibodies that can prevent a second attack of certain infectious diseases. Platelets (also known as thrombocytes), are the smallest blood cells and are important in blood clotting.
The numbers, shapes, and appearance of the various types of blood cell are of great value in the diagnosis of disease (see blood count; blood film).... blood cells
During the chronic phase, symptoms may include fever, night sweats, and weight loss. Visual disturbances, abdominal pain, and priapism may also occur. The symptoms of the more cancerous phase are like those of the acute forms of leukaemia (see leukaemia, acute). The diagnosis is made from blood tests and a bone marrow biopsy. Treatment of the chronic phase includes anticancer drugs. When the disease transforms into the acute phase, treatment is similar to that given for acute leukaemia.... leukaemia, chronic myeloid