Asthma : Precipitating factors

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Asthma

"Precipitating factors"

Precipitating factors
Occupational sensitizers (Next Table)
Over 250 materials encountered at the workplace, accounting for 15% of all asthma cases, give rise to occupational asthma. The causes are recognized occupational diseases in the UK, and patients in insurable employment are therefore

 

Occupational asthma
Cause	Source/Occupation
Low molecular weight (non-IgE related)
Isocyanates	Polyurethane varnishes Industrial coatings Spray painting
Colophony fumes	Soldering/welders Electronics industry
Wood dust Drugs Bleaches and dyes Complex metal salts, e.g. nickel, platinum, chromium High molecular weight (IgE related)
Allergens from animals and insects	Farmers, workers in poultry and seafood processing industry; laboratory workers
Antidotes	Nurses, health industry
Latex	Health workers
Proteolytic enzymes	Manufacture (but not use) of ‘biological’ washing powders
Complex salts of platinum	Metal refining
Acid anhydrides and polyamine hardening agents	Industrial coatings

eligible for statutory compensation provided they apply within 10 years of leaving the occupation in which the asthma developed.
Asthma can be due to:
■ high molecular weight compounds, e.g. flour, organic dusts and other large protein molecules involving specific IgE antibodies, or
■ low molecular weight compounds, e.g. reactive chemicals such as isocyanates and acid anhydrides that bond chemically to epithelial cells to activate them as well as provide haptens recognized by T cells.

The risk of developing some forms of occupational asthma increases in smokers. The proportion of employees developing occupational asthma depends primarily upon the level of exposure. Proper enclosure of industrial processes or appropriate ventilation greatly reduces the risk. Atopic individuals develop occupational asthma more rapidly when exposed to agents causing the development of specific IgE antibody. Non-atopic individuals can also develop asthma when exposed to such agents, but after a longer period of exposure.

Non-specific factors
The characteristic feature of BHR in asthma means that, as well as reacting to specific antigens, the airways will also respond to a wide variety of non-specific direct and indirect stimuli.

Cold air and exercise
Most asthmatics wheeze after prolonged exercise. Typically, the attack does not occur while exercising but afterwards. The inhalation of cold, dry air will also precipitate an attack. Exercise-induced wheeze is driven by release of histamine, prostaglandins (PGs) and leukotrienes (LTs) from mast cells as well as stimulation of neural reflexes when the epithelial lining fluid of the bronchi becomes hyperosmolar owing to drying and cooling during exercise. The phenomenon can be shown by exercise, cold air and hypertonic (e.g. saline or mannitol) provocation tests.

Atmospheric pollution and irritant dusts,
vapours and fumes
Many patients with asthma experience worsening of symptoms on contact with tobacco smoke, car exhaust fumes, solvents, strong perfumes or high concentrations of dust in the atmosphere. Major epidemics have been recorded when large amounts of allergens are released into the air, e.g. soybean epidemic in Barcelona. Asthma exacerbations increase in both summer and winter air pollution episodes associated with climatic temperature inversions. Epidemics of the disease have occurred in the presence of high concentrations of ozone, particulates and NO2 in the summer and particulates, NO2 and SO2 in the winter.

Diet
Increased intakes of fresh fruit and vegetables have been shown to be protective, possibly owing to the increased intake of antioxidants or other protective molecules such as flavonoids. Genetic variation in antioxidant enzymes is associated with more severe asthma.

Emotion
It is well known that emotional factors may influence asthma both acutely and chronically, but there is no evidence that patients with the disease are any more psychologically disturbed than their non-asthmatic peers. An asthma attack is a frightening experience, especially when of sudden and unexpected onset. Patients at special risk of life-threatening attacks are understandably anxious.

Drugs
- Non-steroid anti-inflammatory drugs (NSAIDs). NSAIDs, particularly aspirin and propionic acid derivatives, e.g. indometacin and ibuprofen, have a role in the development and precipitation of asthma in approximately 5% of patients. NSAID intolerance is especially prevalent in those with both nasal polyps and asthma and is not infrequently associated with a triad of asthma, rhinitis and flushing on drug exposure. In susceptible subjects exposure to NSAIDs reveals an imbalance in the metabolism of arachidonic acid. NSAIDs inhibit arachidonic acid metabolism via the cyclo-oxygenase (COX) pathway, preventing the synthesis of certain prostaglandins. In aspirin-intolerant asthma there is reduced production of PGE2 which, in a sub-proportion of genetically susceptible subjects, induces the overproduction of cysteinyl leukotrienes by eosinophils, mast cells and macrophages. In such patients there is evidence for genetic polymorphisms involving the enzymes and receptors of the leukotriene generating pathway (Next Fig.). Interestingly, asthma in intolerant patients is not precipitated by COX-2 inhibitors, indicating that it is blockade of the COX-1 isoenzyme that is linked to impaired PGE2 production.
- Beta-blockers. The airways have a direct parasympathetic innervation that tends to produce bronchoconstriction. There

Arachidonic acid metabolism and the effect of drugs. The sites of action of NSAIDs (e.g. aspirin, ibuprofen) are shown. The enzyme cyclo-oxygenase occurs in three isoforms, COX-1 (constitutive), COX-2 (inducible) and COX-3 (in brain). PG, prostaglandin; BLT, B leukotriene receptor; cysLT, cysteinyl leukotriene receptor.

is no direct sympathetic innervation of the smooth muscle of the bronchi, and antagonism of parasympathetically induced bronchoconstriction is critically dependent upon circulating epinephrine (adrenaline) acting through β2-receptors on the surface of smooth muscle cells. Inhibition of this effect by β-adrenoceptor-blocking drugs such as propranolol leads to bronchoconstriction and airflow limitation, but only in asthmatic subjects. The so-called selective β1-adrenergicblocking drugs such as atenolol may still induce attacks of asthma; their use to treat hypertension or angina in asthmatic patients is best avoided.

Allergen-induced asthma
The experimental inhalation of allergen by atopic asthmatic individuals leads to the development of different types of reaction, as illustrated in next Figure.
- Immediate asthma (early reaction). Airflow limitation begins within minutes of contact with the allergen, reaches its maximum in 15–20 minutes and subsides by 1 hour.
- Dual and late-phase reactions. Following an immediate reaction many asthmatics develop a more prolonged and sustained attack of airflow limitation that responds less well to inhalation of bronchodilator drugs such as salbutamol. Isolated late-phase reactions with no preceding immediate response can occur after the inhalation of some occupational sensitizers such as isocyanates. During and up to several weeks after the exposure, the airways are hyperresponsive, which may explain persisting symptoms after allergen exposure.