Asthma pathophysiology

Asthma is considered a common chronic disorder of the airways that is complex and heterogeneous. Common characteristics include variable airflow obstruction, airway hyperresponsiveness, and underlying inflammation.1,2

Persistent changes in airway structure occur in some patients with asthma. These include subbasement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis. Compare the differences between a normal airway and one with asthma in the diagram below.1

Normal Airway

During Asthma Symptoms

Reprinted from Holgate ST, Sly PD. Asthma pathogenesis. In: Adkinson Jr NF, Bochner BS, Burks AW, et al, eds. Middleton's Allergy Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:812-842.

Cellular inflammation

Cells such as epithelial, fibroblasts, and smooth muscle cells reside in the airways and are recognized as modulators of inflammation and remodeling. This inflammation has been categorized into eosinophilic, neutrophilic, and/or paucigranulocytic. The concomitant presence of both eosinophils and neutrophils (mixed cellularity) has been reported to be associated with the most severe disease.3

Obstruction and airway hyperresponsiveness

Structural alterations, such as a thickened epithelium, affect airway mechanics while also contributing to inflammatory processes. In addition, studies have linked an increased amount of airway smooth muscle to asthma severity, airflow obstruction, and bronchial hyperresponsiveness.3

Airway Remodeling and Inflammation

As asthma becomes more severe, the pathology associated with remodeling and inflammation becomes increasingly important4

Remodeling is defined as structural changes in the airway walls that stem from inflammatory changes.5

In severe asthma, exaggerated airway remodeling may be seen. This remodeling includes subepithelial thickening of the bronchial reticular layer and in the small airways.3

In time, remodeling can compromise the efficacy of bronchodilators and oral corticosteroids and cause more severe exacerbations.3

Altogether, airway obstruction may result from a combination of5:

  • Bronchoconstriction as a consequence of active constriction of airway smooth muscle
  • Airway wall thickening associated with inflammation and remodeling
  • Luminal obstruction caused by hypersecretion of mucus that may be thickened due to dehydration

Research has suggested that in the clinical setting, low post-bronchodilator FEV1/FVC ratio and airway wall thickening on computed tomography (CT) may serve as remodeling markers6

References: 1. National Institutes of Health. Section 2, Definition, pathophysiology and pathogenesis of asthma, and natural history of asthma. In: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute (US); 2007. www.ncbi.nlm.nih.gov/books/NBK7223/. Accessed June 22, 2017. 2. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2017. www.ginasthma.org. Accessed July 26, 2017. 3. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343-373. 4. Holgate ST, Sly PD. Asthma pathogenesis. In: Adkinson Jr NF, Bochner BS, Burks AW, et al, eds. Middleton's Allergy Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:812-842. 5. Kumar RK, Jeffery PK. Pathology of asthma. In: Adkinson Jr NF, Bochner BS, Burks AW, et al, eds. Middleton’s Allergy Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:986-999. 6. Chae EJ, Kim T-B, Cho YS, et al. Airway measurement for airway remodeling defined by post-bronchodilator FEV1/FVC in asthma: investigation using inspiration-expiration computed tomography. Allergy Asthma Immunol Res. 2011;3(2):111-117.

 

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