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:
1 Airflow limitation which is usually reversible spontaneously or with treatment. In chronic asthma inflammation may lead to irreversible airflow limitation.
2 Airway hyperresponsiveness to a wide range of stimuli.
3 Inflammation of the bronchi with eosinophils, T lymphocytes and mast cells with associated plasma exudation, oedema, smooth muscle hypertrophy, mucus plugging and epithelial changes.
The underlying pathology in preschool children may be different in that they may not exhibit appreciable bronchial hyperreactivity. There is no evidence that chronic inflammation is the basis for the episodic asthma associated with viral infections.
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, for example, New Zealand, but being much rarer in Far Eastern countries such as China and Malaysia. Long-term follow- up in developing countries suggests that the disease may become more frequent as individuals become more ‘Westernized’. Studies of occupational asthma suggest that a high percentage of the work-force, perhaps up to 20%, may become asthmatic if exposed to potent sensitizers.
Asthma can be divided into:
• Extrinsic-implying a definite external cause
• Intrinsic or cryptogenic-when no causative agent can be identified
EXTRINSIC ASTHMA occurs in atopic individuals who show positive skin-prick reactions to common inhaled allergens. Positive skin tests to inhalant allergens are shown in 90% of children with asthma, whereas only 50% of adults show this phenomenon. Eczema is often seen in childhood.
INTRINSIC ASTHMA often starts in middle age. Nevertheless, many show positive skin tests and on close questioning give a history of respiratory symptoms compatible with childhood asthma.
This classification is of little value in clinical practice. Non-atopic individuals may develop asthma in middle age from extrinsic causes such as sensitization to occupational agents or aspirin intolerance, or because they were given J3-adrenoreceptor-blocking agents for concurrent hypertension or angina. Extrinsic causes must be considered in all cases of asthma and, where possible, avoided.
AETIOLOGY AND PATHOGENESIS
There are two major factors involved in the development of asthma and many other stimuli that can precipitate attacks.
Atopy and allergy
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 now best used to describe those individuals who readily develop antibodies of IgE class against common materials present in the environment. Such antibodies are present in 30-40% of the population, and there is a link between serum IgE levels and both the prevalence of asthma and airway responsiveness to histamine or methacholine. Genetic and environmental factors affect serum IgE levels. Whilst the precise location of the genes controlling IgE production remains to be determined, early childhood exposure to allergens and maternal smoking have an important influence on IgE production. The allergens involved are similar to those in rhinitis, though the particle size of pollens (>20 /Lm) means that they are much more likely to cause conjunctivitis, rhinitis and pharyngitis than asthma. Allergens from the faecal particles of the house-dust mite are the most important extrinsic cause of asthma worldwide. The fungal spores from A. fumigatus give rise to a complex series of lung disease, including asthma.
Increased responsiveness of the airways of the lung (airway hyperreactivity)
Bronchial reactivity can be demonstrated by asking the patient to inhale gradually increasing concentrations either of histamine or methacholine (bronchial provocation tests). This induces a transient episode of airflow limitation in susceptible individuals (approximately 20% of the population); the dose of the agonist (provocation dose) necessary to produce a 20% fall in FEV, is known as the PD2oFEV,. Patients with clinical symptoms of asthma respond to very low doses of methacholine, i.e. they have a low PD20FEV, «11 /Lmol). In general, the greater the degree of hyperreactivity, the more persistent the symptoms and the greater the need for treatment. Some patients also react to methacholine but at higher doses and include those with:
• Attacks of asthma only on extreme exertion
• Wheezing or prolonged periods of coughing following a viral infection
• Cough variant asthma
• Problems with asthma only during the pollen season
• Allergic rhinitis, but not complaining of any lower respiratory symptoms until specifically questioned
• Some subjects with no respiratory symptoms Although the degree of hyperreactivity can itself be influenced by allergic mechanisms, its pathogenesis and mode of inheritance remain to be elucidated.