Asthma Knowledge Centre
Pathophysiology
The asthmatic response
The asthmatic response is divided into early and late phases (Figure 1 below).1
Early phase
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The early phase response results from activation of cells bearing allergen-specific IgE, in particular, mast cells and macrophages.1, 2 Cross-linkage of cell-bound IgE results in the release of newly formed mediators, which, in turn, initiates the inflammatory cascade.3
Late phase
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Activated eosinophils release enzymes and mediators that can damage bronchial epithelium, induce smooth-muscle contraction, enhance microvascular permeability, increase airway hyperreactivity and contribute to airway remodeling.1 However, some studies have shown that reducing eosinophilia alone in patients with asthma does not abolish airflow limitation or airway hyperreactivity, which emphasizes the multifactorial nature of asthmatic inflammation4
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Lymphocytes are thought to play a major role and direct ongoing inflammation by the release of T-helper type 2 cytokines, several of which have the potential to modulate airway inflammation1, 5
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Macrophages and neutrophils are found in the airways during the late reaction, but their numbers are variable. Macrophages play a fundamental role in specific immunity and a major role in chronic inflammation1
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The recruitment of inflammatory cells from blood vessels to the airway mucosa occurs by transmigration across the endothelium as a result of adhesive interactions between circulating inflammatory and microvascular endothelial cells via the production of pro-inflammatory mediators, cytokines and chemokines, as well as the expression of cell surface adhesion molecules.1 Survival factors (cytokines and chemokines), released in situ, prolong the inflammatory response by reducing apoptosis1
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The cells and mediators involved are part of a normal repair process. When these are chronically present, however, abnormal structural alterations are produced through angiogenesis, thickening of the basement membrane, fibrosis and smooth-muscle hypertrophy1
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Constitutive elements from the airway wall contribute to the remodelling process1
The consequences of inflammation during the early and late phases of the asthmatic response are airflow obstruction and hyperreactivity which lead to the characteristic symptoms of asthma. The complex interaction among inflammatory cells, mediators and constitutive components of the respiratory mucosa lead to a decrease in lung function, as evidenced by decreases in peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) (Figure 1).
Figure 1. Early and late asthmatic reactions.
PEF=peak expiratory flow; FEV1=forced expiratory volume in 1 second
References:
1. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and
remodeling. Am J Respir Crit Care Med 2000;161:1720–1745.
2. Kay AB. Inflammatory cells in bronchial asthma. J Asthma 1989;26:335–344.
3. GINA. Global Initiative for Asthma. www.ginasthma.com. 2005.
4. Bryan SA, O’Connor BJ, Matti S, Leckie MJ, Kanabar V, Khan J, et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2149–2153.
5. Kay AB. The role of T lymphocytes in asthma. Chem Immunol Allergy 2006;91:59–75.