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Asthma pathology and development 

What is asthma?

Asthma’s clinical manifestations are related to airflow obstruction and airway hyperresponsiveness. 1These are worse in both severe and uncontrolled asthma. Symptoms include dyspnoea, wheeze, cough, chest tightness and nocturnal awakenings, which can be persistent. 2-3Long-term manifestations of asthma include exacerbations, loss of lung function, impairment of quality of life and comorbidities. 3

For many years, asthma has been considered a single disease. However, recent studies have shown that it is in fact a complex, heterogeneous clinical syndrome, 4-6with common characteristic symptoms of variable airflow obstruction, airway hyperresponsiveness and cellular inflammation. 5

Airway inflammation, injury and injury/repair process are critical components of asthma pathogenesis. 5Compare the differences between a normal airway and one with asthma in the diagram below.

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Asthma pathology

Overview of a normal airway showing healthy smooth muscle, mucous lining, lumen and blood vessels.

Adapted from Holgate, et al. 2013. 5

Overview of airway with asthma, a complex heterogeneous clinical syndrome. Blood vessels infiltrated by immune cells, excess mucus, contracted smooth muscle with inflammation and swelling, and decreased lumen diameter.

Adapted from Holgate, et al. 2013.5

Asthma is a developmental disease

Asthma may develop in childhood or adulthood. Early-onset asthma has been linked to allergic comorbidities and a family disease history. 2Patients developing asthma in adulthood tend to be female, have persistent eosinophilic inflammation and less genetic predisposition. 2These differences underpin the evidence that asthma develops from complex interactions between environmental exposures and underlying genetic factors. 5

Many features of asthma are thought to occur following environmental exposure during foetal development or shortly after birth. 5The consequences of these exposures may vary, depending on the developmental stage of the respiratory and immune systems as well as a number of underlying genetic factors. 5

A number of cellular components are involved in asthma development, many of which overlap. Allergen exposure is often a factor, which provokes inflammatory activity in innate immune cells. This is followed by crosstalk with the adaptive immune system. The result is the defining pathologic features of asthma: a Th2 cytokine response, smooth muscle constriction and tissue remodelling. 5-6Remodelling is irreversible and occurs downstream of several complex processes, with the end result of basement membrane thickening, smooth muscle hypertrophy, fibrosis, goblet cell hyperplasia and reduced airway calibre. 5-6

Regardless of the pathways involved in individual patients, there is a general agreement that airway inflammation and injury, as well as the remodelling that occurs in some patients, are likely critical components of asthma pathogenesis. 5-6

The pathophysiology of asthma

Asthmatic inflammation is generally characterised by the presence of eosinophils and related mediators. These are responsible for the airway inflammation, injury and the tissue remodelling processes that are critical components in asthma pathogenesis. 5

Asthma is associated with a particular type of airway inflammation that increases sensitivity to various triggers. The specific pattern of airway inflammation in asthma is associated with airway hyperresponsiveness, which is correlated with variable airflow obstruction. The pattern of inflammation in asthma is characteristic of allergic diseases, with similar inflammatory cells seen in the nasal mucosa in rhinitis. 6

References

  1. Kumar RK, Jeffery PK. Pathology of Asthma. Middleton's Allergy: Principles and Practice. Saunders Elsevier, Philadelphia, PA, USA: 2014.
  2. Chung KF, et al. Eur Respir J 2014;43:343–73.
  3. GINA 2016 © 2016 Global Initiative for Asthma, all rights reserved.  Use is by express license from the owner. www.ginasthma.org (Last accessed December 2016).
  4. Wenzel SE. Nat Med 2012;18:716–25.
  5. Holgate ST, Sly PD. Asthma Pathogenesis. Middleton's Allergy: Principles and Practice. Saunders Elsevier, Philadelphia, PA, USA: 2014.
  6. Barnes PJ. Asthma in Harrison's Principles of Internal Medicine. Chapter 254. Available at http://accessmedicine.mhmedical.com/ (Last accessed August 2015).