Contents of the training materials

Aetiology and pathogenesis of the disease.

The aetiology of asthma is complex, and multiple environmental and genetic determinants are implicated. The hygiene hypothesis proposes that decreased infections in early life bias the immune system towards an allergic phenotype. T lymphocytes may differentiate into two distinct subsets: Th1 and Th2. In infancy, a shift occurs from the in utero Th2 bias towards a Th1 response necessary for fighting viral and bacterial infection. A reduction in childhood infections favours persistence of a Th2 bias (characterised by cytokines such as interleukins 4, 5 and 13), directing the immune system towards an allergic type of response. In support of this hypothesis, day care attendance (which presumably increases exposure to childhood infections) is associated with lower rates of atopy, wheeze and asthma in later childhood. Other infections, however, such as respiratory syncytial virus, appear to increase the risk of developing asthma and the validity of this hypothesis (including the ability to distinguish Th1 and Th2 cells clearly in humans) has been challenged.

Causes.

• Factors that can contribute to asthma or airway hyperreactivity may include any of the following:
• Environmental allergens (House dust mites, animal allergens [especially cat and dog], cockroach allergens, and fungi are most commonly reported.)
• Viral respiratory infections
• Exercise; hyperventilation
• Gastroesophageal reflux disease (GERD)
• Chronic sinusitis or rhinitis
• Aspirin or nonsteroidal anti-inflammatory drug hypersensitivity, sulfite sensitivity
• Use of beta-adrenergic receptor blockers (including ophthalmic preparations)
• Obesity (Based on a prospective cohort study of 86,000 patients, those with an elevated body mass index are more likely to have asthma.)
• Environmental pollutants, tobacco smoke
• Occupational exposure
• Irritants such as household sprays and paint fumes
• A variety of high and low molecular weight compounds are associated with the development of occupational asthma such as insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and fluxes.
• Emotional factors or stress
• Perinatal factors (Prematurity and increased maternal age increase the risk for asthma; breastfeeding has not been definitely shown to be protective. Both maternal smoking and prenatal exposure to tobacco smoke also increase the risk of developing asthma.)

Pathophysiology

The inhalation of an allergen in a sensitised atopic asthmatic patient results in a two-phase bronchoconstrictor response. The inhaled allergen rapidly interacts with mucosal mast cells via an IgE-dependent mechanism, resulting in the release of mediators such as histamine and the cysteinyl leukotrienes with resulting bronchoconstriction. In persistent asthma a chronic and complex inflammatory response ensues, which is characterised by an influx of numerous inflammatory cells, the transformation and participation of airway structural cells, and the secretion of an array of cytokines, chemokines and growth factors.

Airway hyper-reactivity (AHR) is integral to the diagnosis of asthma and appears to be related, but not exclusively so, to airway inflammation. Other factors are likely to be important including the behaviour of airway smooth muscle, the degree of airway narrowing and the influence of neurogenic mechanisms.

With increasing severity and chronicity of the disease, remodelling of the airway occurs, leading to fibrosis of the airway wall, fixed narrowing of the airway and a reduced response to bronchodilator medication.

Clinical features

Asthma is not a uniform disease but a dynamic clinical syndrome with a variety of features. Typical symptoms include recurrent episodes of wheezing, chest tightness, breathlessness and cough. Common precipitants include exercise, particularly in cold weather, exposure to airborne allergens or pollutants, and viral upper respiratory tract infections (beware the cold that 'goes to the chest' or takes more than 10 days to clear). Patients with mild intermittent asthma are usually asymptomatic between exacerbations which occur during viral respiratory tract infections or after exposure to allergens. In persistent asthma the pattern is one of chronic wheeze and breathlessness.

Asthma characteristically displays a diurnal pattern, with symptoms and PEF being worse in the early morning. Particularly when asthma is poorly controlled, symptoms such as cough and wheeze disturb sleep and have led to the use of the term 'nocturnal asthma'. Cough may be the dominant symptom in some patients and the lack of wheeze or breathlessness may lead to a delay in reaching the diagnosis of so-called 'cough-variant asthma'.

In some circumstances the appearance of asthma relates to the use of medications. Beta-adrenoceptor antagonists (β-blockers-even when administered topically as eye drops) may induce bronchospasm. Aspirin and other non-steroidal anti-inflammatory drugs are associated with asthma in about 10% of patients. This is believed to reflect a shift in the metabolism of arachidonic acid from the cyclo-oxygenase pathway generating prostaglandins, towards the lipo-oxygenase pathway generating cysteinyl leukotrienes. Aspirin-sensitive asthma is often associated with rhinosinusitis and nasal polyps.

Occupational asthma is now the most common form of occupational respiratory disorder and accounts for around 5% of all adult-onset asthma. This should be considered in all adult asthmatics of working age, particularly if symptoms improve during time away from work, e.g. weekends or holidays. Atopic individuals and smokers appear to be at increased risk. Early diagnosis and removal from exposure leads to a significantly improved prognosis and may result in cure. The recognition of occupational asthma has important medico-legal implications and should prompt screening of the workplace as other employees may also have developed the disease.

An important minority of patients appear to have a particularly severe form of asthma; this appears to be more common in women. Allergic triggers appear to be less important and airway neutrophilia predominates.

How Airways Narrow

During an asthma attack, the smooth muscle layer goes into spasm, narrowing the airway. The middle layer swells because of inflammation, and more mucus is produced. In some segments of the airway, the mucus forms clumps that nearly or completely block the airway. These clumps are called mucus plugs.

Date: 2016-06-13; view: 6