Pathophysiology

Airway Inflammation
Infectious agents constantly enter the body via the respiratory system. The bronchi have several protective methods against these invaders. These include:


-recruitment of inflammatory cells from the bloodstream into the bronchial wall, where they directly attack the invading organisms and secrete inflammatory chemicals that are toxic to the organisms
-swelling of the bronchial wall
-mucus secretion
-constriction of the airway.

In asthma, these inflammatory actions occur in the bronchi when no serious infection, toxin, or other inhaled threat to the body exists.
Airway inflammation in asthma is:

-a direct response of the immune system to a trigger
-a cascade of immunologic events that includes inflammatory cells and mediators
-an immune-mediated process that leads to inflammatory changes in the airway, including eosinophil recruitment and airway edema.



Pathophysiology of the Airway in Asthma

A cross-section of a normal airway is shown in the figure below. The lumen is free of significant mucus. The single layer of ciliated epithelial cells lines and protects the bronchial wall. The mucous gland provides a protective layer of mucus above the epithelial cells. There are few eosinophils in the bronchial wall.


The following figure depicts some of the histologic features of airway inflammation. Plasma leakage from blood vessels contributes to bronchial wall edema, which results in thickening of the bronchial wall. Eosinophils migrate from the bloodstream into the bronchial wall and the airway lumen and can release eosinophil cationic protein and leukotrienes. Enlarged mucus glands secrete excess mucus that can plug the airway lumen.



As the airway walls thicken due to these inflammatory reactions, the amount of airway narrowing produced by a given amount of smooth muscle contraction in asthma is much greater than that in a normal airway. Thus, even a small contraction of bronchial smooth muscle can lead to dramatic increases in airway resistance when the bronchial walls are already thickened from the actions of inflammatory cells and airway edema.




Bronchoconstriction
Inhalation of an allergen solution by a patient with allergic asthma causes prompt and significant bronchoconstriction. After this bronchial allergen challenge, there is a rapid decline in forced expiratory volume in 1 second (FEV1) that begins within 15 minutes and generally subsides within the first hour . This bronchial manifestation of immediate hypersensitivity has been termed an early asthmatic reaction (EAR), or the early phase response. After this phase resolves (spontaneously or with a beta-agonist, if needed), the FEV1 reaches a level that is at or close to the pre-challenge baseline.










In about 50% of patients, there can be a spontaneous return of bronchoconstriction that occurs several hours after the allergen challenge (and after the EAR has resolved). This late phase response usually occurs 6-24 hours after exposure to the allergen and is termed the late asthmatic response (LAR). This late decline in FEV1 may be less severe than during the EAR but is generally more prolonged, lasting several hours.
The EAR results from binding of inhaled allergen to mast cell membrane-bound IgE with subsequent release of mediators (e.g., histamine, leukotrienes, and prostaglandins). Among these mediators, the cysteinyl leukotrienes appear to account for a significant part of the early bronchoconstrictor response.




Inflammatory and Bronchoconstriction Events of the Early Phase of an Acute Asthmatic Response to Allergen Exposure


The LAR to an allergen is typified not only by a decline in FEV1 but also by the influx of inflammatory cells, most notably eosinophils, and airway edema. The intensity of LAR inflammation correlates with the degree of airflow obstruction that occurs during the LAR. Note that the airflow obstruction of the LAR usually lasts longer, as much as several hours or more.



Inflammatory and Bronchoconstriction Events of the Late Phase of an Acute Asthmatic





The LAR often resembles asthma, which is a chronic inflammatory disease. It is possible that repeated or prolonged episodes of LAR may approximate the events in the airways in both chronic allergic and nonallergic asthma.





"Airway remodeling"
The term airway remodeling is widely used to refer to the development of specific structural changes in the airway wall in asthma accompanying long-standing and severe airway inflammation. Airway remodeling and fibrosis may be the cause of "fixed" airflow obstruction in asthma that is not reversible with steroids, bronchodilators, or both. Interest has especially been focused on subepithelial collagen deposition, myofibroblast accumulation, airway smooth muscle hyperplasia and hypertrophy, mucous gland and goblet cell hyperplasia, and epithelial disruption.






Signs and Symptoms

Most asthma attacks are preceded by warning signs. Recognizing these warning signs and treating symptoms early can help prevent attacks or keep them from becoming worse.

Warning signs and symptoms of asthma in adults may include:


-Increased shortness of breath or wheezing
-Disturbed sleep caused by shortness of breath, coughing or wheezing
-Chest tightness or pain
-Increased need to use bronchodilators — medications that open up airways by relaxing the surrounding muscles
-A fall in peak flow rates as measured by a peak flow meter, a simple and inexpensive device that allows you to monitor your own lung function


Children often have an audible whistling or wheezing sound when exhaling and frequent coughing spasms.

Chris