Pathophysiology of asthma
Atopic individuals produce excessive amounts of the antibody immunoglobulin E (IgE), usually triggered by allergens such as house dust mite, tree pollens and animal dander. The ‘atopic triad’ of asthma, allergic rhinitis and eczema are the most common manifestations of allergic disease, and are frequently comorbid.
Both genetic and environmental factors will influence the development of atopic disease in an individual. A positive family history of asthma will therefore heighten greatly the chances of diagnosis, as may environmental exposure to allergens, dietary factors and microbes and maternal smoking.
Any individual will constantly inhale infectious agents during the process of breathing and lung tissues employ several protective mechanisms. Inflammatory cells are attracted from the circulation into the bronchial wall, where they attack and then secrete inflammatory chemicals that are toxic to the organisms. This action causes swelling of the bronchial wall, increased mucus secretion and constriction of the airway.
In asthma, this inflammatory response occurs in the bronchi when no serious infection, toxin, or other inhaled threat to the body exists.Airway inflammation in acute asthma is a direct response of the immune system to a trigger (allergen) causing a cascade of immunologic events that includes inflammatory cells and mediators and an immune-mediated process that leads to inflammatory changes in the airway, including eosinophil recruitment and airway oedema.
It is thought that chronic inflammation results in the airways becoming hyper-responsive to stimuli causing bronchoconstriction (and obstruction to airflow) much more readily than is normal. This airway obstruction is either completely or partially reversible either spontaneously or in response to therapy (bronchodilator or corticosteroid). However, chronic cellular infiltration of the airway walls, (by T-helper cells, eosinophils, mast cells and also CD-4 cells and neutrophils), is now known to cause epithelial damage leading to irreversible airway remodelling and permanent hypertrophied and narrowed airways.
The allergic response in the airway tissues is driven by T-helper cells that stimulate B-lymphocytes and the production of large amounts of IgE. The IgE binds to mast cell receptors in the upper and lower airway and when the individual is subsequently re-exposed to the allergen or trigger, it binds to the IgE causing a cascade of inflammatory mediator release from the mast cell. These include histamine, leukotrienes, cytokines and chemokines.
An early phase allergic response occurs almost immediately, peaking at around 30 minutes and subsiding after an hour. Asthma symptoms may be wheeze, cough, dyspnoea and chest tightness and reduced peak flow. In concurrent rhinitis, the individual may experience nasal itching, obstruction and rhinorrhoea (runny nose).
The late phase response is driven by cytokines and chemokines and causes further inflammatory changes. These cells trigger the production in bone marrow of white blood cells including eosinophils which flood the upper and lower airways secreting further inflammatory markers and recruiting further leucocytes. This inflammatory response is longer lasting and causes the bronchial smooth muscle to become hyper-reactive and to constrict excessively in the presence of the trigger.
During an asthma attack individuals will normally be able to maintain perfusion as they naturally hyperventilate, keeping carbon dioxide levels in a normal range. However, if the exacerbation is severe, the exceptional extent of bronchoconstriction causes considerable air-trapping, the respiratory muscles are unable to cope with the inspiratory effort required and the individual will rapidly become exhausted with the work of breathing. In this situation, the resulting hypoxaemia and hypercapnia will deteriorate if untreated leading to respiratory and cardiac arrest.
Image used with permission: National Institute of Allergy and Infectious Diseases (NIAID) (US)