Asthma Knowledge Centre
Asthma
Pathophysiology
The pathophysiology of asthma is a complex cascade of interactions among inflammatory cells, mediators and constitutive components of the respiratory mucosa (Figure 1). The underlying inflammatory processes involve both the large and small airways.
Figure 1. Schematic overview of asthma pathophysiology
APC=antigen presenting cell
Inflammation
Microscopic analyses of the larger airways have shown infiltration of eosinophils and lymphocytes, as well as vasodilation, angiogenesis, disruption of the bronchial epithelium, thickening of the basement membrane and smooth-muscle hypertrophy (Figure 2).1 Although access to the smaller airways is difficult, evidence of airway inflammation has also been described in distal airways in autopsies of patients with asthma.
Figure 2. Histologic sections of intrapulmonary bronchi showing the inflammatory effects of asthma on the airways (A: normal subject without a history of asthma, B: subject with fatal asthma)1
Reproduced with permission from Bousquet J et al. From bronchonstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000; 161(5):1720–1745. Copyright American Thoracic Society, 2000.
It is notable that these changes are seen at all levels of asthma severity, including patients with mild, intermittent asthma. Such findings indicate that inflammation, and its effects, begin in milder forms of asthma, sometimes before symptoms develop.2, 3,4
Remodelling
In parallel with the chronic inflammatory process, injury to the bronchial epithelium stimulates a ‘repair’ process that results in structural and functional changes, often described as airway remodeling. The process of remodeling involves changes in connective tissue deposition and various alterations in the airway structure.2, 1 Core elements driving the airway remodeling process are a combination of epithelial damage, prolonged epithelial repair, overproduction of profibrotic growth factors, and proliferation and differentiation of fibroblasts into myofibroblasts.2, 1
For decades asthma was considered a condition of reversible air-flow obstruction. In the majority of patients, complete reversibility of longstanding abnormalities in spirometry measures can be seen after treatment with ICS.2 However, in many patients there is evidence of residual airway obstruction, despite therapy with ICS, and even asymptomatic patients can show residual obstruction, which may be due to airway remodeling.2
Evidence suggests that loss of airway function, presumably due to remodeling, occurs even in mild asthma of recent onset. However, this can be prevented by the early use of regular, appropriately dosed ICS therapy.2
Glucocorticosteroids are currently regarded as the most effective anti-inflammatory medications for asthma, and ICS are the recommended treatment for patients with persistent asthma.5 Studies have demonstrated the efficacy of ICS in improving lung function, decreasing airway hyperresponsiveness, reducing symptoms, improving quality of life, reducing the frequency and severity of exacerbations, controlling airway inflammation and reducing asthma morbidity.5
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. GINA. Global Initiative for Asthma. www.ginasthma.com. 2005.
3. Boulet LP, Turcotte H, Laviolette M, Naud F, Bernier MC, Martel S, et al. Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids. Am J Respir Crit Care Med 2000;162:1308–1313.
4. Vignola A, Chanez P, Campbell AM, Souques F, Lebel B, Enander et al. Airway inflammation in mild intermittent and in persistent asthma. Am J Respir Crit Care Med 1998;157:403–409.
5. GINA. Global Initiative for Asthma. www.ginasthma.com. 2006