Pathophysiology of Asthma

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy

Asthma is a common and well known ailment affecting the respiratory tract which is characterized by airway hyper-responsiveness to a multitude of stimuli. This chronic, relapsing, remitting disease can occur in various degrees of severity and can be severely disabling. The magnitude of the burden of asthma is reflected by the fact that approximately 4-5% of the population of the United States is affected by this disease, with almost 10-11 million people having an acute episode in the year 1998, as estimated by the Centers for Disease Control and Prevention (McFadden, 2005).

Asthma has both physiologic and clinical manifestations. The physiologic manifestations include a generalized narrowing of the airways, leading to a decrease in the air flow rates through the tracheobronchial tree during the expiratory phase of respiration. This may or may not lead to an increase in the functional residual capacity as a result of the trapping of gases within the airways (Slovis & Brigham, 2000).  This thereby leads to the clinical triad of the presentation of asthma viz. paroxysmal dyspnea, bouts of cough and wheezing (McFadden, 2005). This disease is episodic in nature whereby there are periods of acute exacerbations, lasting from minutes to hours and sometimes even days (e.g. in status asthmaticus), which are separated by symptom free intervals (McFadden, 2005).

The age of onset of this disease is variable but onset predominantly occurs in childhood with about 50% of the total patients presenting before the age of ten years (McFadden, 2005). The male to female ratio varies according to the age group with twice as many males being affected as females under the age of 10, while beyond the age of 30 this discrepancy amongst the sexes disappears (McFadden, 2005).

The etiology of asthma is diverse and a complex interplay between genetic and environmental factors has been implicated in the pathogenesis of this disease. The most of important genetic factor which predisposes individuals to asthma is atopy. Patients of asthma often have a personal or family history of atopy or allergic manifestations which include allergic rhinitis, atopic dermatitis (eczema) and urticarial reactions. These individuals have other concomitant findings including increased serum levels of IgE and the development of the classic wheal and flare reaction upon exposure to certain allergens.

This type of asthma is referred to as the allergic type. On the other hand, individuals who do not have any history of atopy and normal IgE levels, have a variant of asthma which is termed as nonatopic or idiosyncratic asthma. The third, less common type which exists is the mixed type which includes features of both the allergic and nonatopic type (McFadden, 2005). The environmental factors which are involved vary amongst individuals and can range from viruses to occupational exposures to food and air borne allergens (McFadden, 2005).

Asthma is an obstructive airway disease which is characterized by increased resistance of the small airways of the tracheobronchial tree which occurs as a consequence of airway hyper-responsiveness to a multitude of stimuli. There are two main factors which influence the flow of air through the tracheobronchial tree, viz. the driving pressure of the incoming gases and the airway resistance. The airflow is directly proportional to the driving pressure while it has an inverse relationship with the airway resistance.

Bronchoconstriction is a normal airway response when noxious stimuli are encountered. However, in asthmatic individuals, this response is exaggerated and exposure to an allergen leads to extensive smooth muscle contraction leading to a decrease in airway diameter and hence an increase in the airway resistance. This increase in the airway resistance, therefore, leads to a decrease in the flow of air through the tracheobronchial tree (Slovis & Brigham, 2000).

There are two other major factors apart from airway hyper responsiveness which contribute towards the narrowing of the airways. These include mucosal edema and an increase in the production of mucus by the goblet cells, both of which occur as a consequence of airway inflammation. Therefore, the three most important factors which are implicated in the pathophysiology of asthma are: airway hyperreactivity, mucosal edema and increased production of mucus (Slovis & Brigham, 2000).

Moreover, apart from these acute changes, there are also long term changes in the tracheobronchial trees of asthmatic individuals. These include hypertrophy of the bronchial smooth muscles and goblet cells, loss of ciliated epithelial cells which leads to an impaired ability to clear the bronchial secretions and mucosal plugging, hyperplasia and congestion of the blood vessels located in the airway mucosal and submucosal layers, infiltration of eosinophils in the bronchial wall and basement membrane thickening (McFadden, 2005).

The pathogenesis of asthma involves a variety of inflammatory cells and mediators. In normal individuals, there exists a balance between the production of pro-inflammatory and inhibitory cytokines. In asthmatic individuals, this balance is tilted in the favor of pro-inflammatory cytokines (e.g. cytokines, leukotrines and bradykinins) resulting in the excess production of these mediators and hence persistent inflammation of the tracheobronchial tree (Slovis & Brigham, 2000). The most important inflammatory cells which are involved in the pathophysiology of asthma include mast cells, eosinophils, lymphocytes and the epithelial cells lining the airways. These cells are involved in the initiation and maintenance of an inflammatory response and the production of various mediators which may either be preformed or newly synthesized on encountering the allergen.

Eosinophils play an important role in the inflammatory response since they are involved in the production of leukotrines, oxygen free radicals and chemotactic factors, and lead to disruption of the normal protective epithelial barrier and secretory functions. Moreover, T-Lymphocytes, in particular the TH2 subset, are also of vital importance in the inflammatory response since they are involved in the production of important cytokines including IL-4 and IL-5. IL-4 is responsible for the activation of the humoral arm of the immune response leading to the production of IgE antibodies while IL-5 is involved in the recruitment and proliferation of eosinophils (McFadden, 2005).

There is a variety of stimuli and allergens which can trigger the inflammatory response in asthmatic individuals. These include pollen, airborne allergens, pharmacologic agents such as aspirin and β adrenergic antagonists, occupational stimuli such as exposure to wood dust, latex and industrial chemicals and even viral respiratory tract infections. The acute exacerbation of asthma in response to an allergen includes an IgE mediated response involving the mast cells and the T and B lymphocytes. On the first encounter with an allergen, there is processing of the antigen by the dendritic cells residing in the airway epithelium.

These antigens are then presented to the T lymphocytes, which leads to their differentiation into the TH2 subset and the production of IgE antibodies. The IgE hence generated, circulates in the blood and binds to the mast cells. On subsequent exposure to the allergen, these IgE antibodies are stimulated and lead to mast cell degranulation causing an immediate immune response whereby preformed mediators stored in mast cell vesicles are released. There is another subsequent late phase of the immune response which occurs six to eight hours later whereby newly synthesized immune mediators are released (McFadden, 2005).

As mentioned above, the clinical presentation of asthma includes the classic triad of dyspnea, cough and wheezing (often referred to as sine qua non). The cough is usually initially non-productive but towards the end of the episode there is presence of thick, stringy mucus. In the distal airways, the mucus is often present in the form of casts which are termed as Curschmann’s spirals and microscopic examination reveals the presence of eosinophils and Charcot-Leyden crystals. The wheezing is present in both phases of respiration with the expiratory phase being characteristically prolonged.

There may also be associated symptoms of tachypnea, tachycardia and mild systolic hypertension. Over the course of the disease, there is over inflation of the lungs resulting from increased residual volume and hence an increase in the anterioposterior diameter of the chest. On clinical examination, the most pertinent findings include the use of accessory muscles of ventilation including the sternocleidomastoid and a paradoxical pulse (McFadden, 2005).

On the basis of the frequency and severity of symptoms, asthma has been classified into four major categories viz. mild intermittent (symptoms present ≤2 days/week and ≤2 nights/month), mild persistent (symptoms present >2 days/week but < 1 per day and <2 nights/month), moderate persistent (symptoms present daily and > 1 night per week) and severe persistent (continua daytime symptoms and frequent night time symptoms). This classification has important implications in the treatment of asthma which is done in a stepwise manner based on the severity of the symptoms (McFadden, 2005).

The treatment of asthma does not only include pharmacologic intervention but also patient education with regard to lifestyle modification and avoidance of allergens (Slovis & Brigham, 2000). The two main categories of pharmacologic agents used in the management of asthma include those which are required for the acute resolution of symptoms including β-adrenergic agonists, anticholinergics and methylxanthines, and those required for long term control of inflammation including glucocorticoids, long acting β2 agonists, mast cell stabilizers and leukotrines modifiers (McFadden, 2005).

In conclusion, asthma is an episodic, chronic, relapsing, remitting disease affecting the small airways of the tracheobronchial tree which is brought about by airway hyperressponsiveness to a variety of stimuli, mucosal edema and increased mucous production leading to the clinical triad of paroxysmal dyspnea, cough and persistent wheezing. Asthmatic exacerbations are often short-lived, resolving either simultaneously or as a result of pharmacologic intervention and the patient is relatively symptom free between the episodes. The management of asthma consists of both patient education and pharmacologic intervention and the symptoms can be kept in check by the use of combination of both these approaches.

References

  • McFadden, E. (2005). Asthma. In Harrison’s Principles of Internal Medicine (pp. 1508-1516). McGraw Hill.
  • Slovis, B. S., & Brigham, K. L. (2000). Obstructive Lung Disease. In T. Andreoli, Cecil Essentials of Medicine (pp. 185-193). W.B. Saunders Company.

David from Healtheappointments:

Hi there, would you like to get such a paper? How about receiving a customized one? Check it out https://goo.gl/chNgQy