Asthma
| Overview |
|---|
- Asthma is a disease thought to be caused by excessive responsiveness of the airways to particular stimuli. This airway hyper-responsiveness manifests as episodic increases in airway resistance that result in transient obstructive patterns of airflow, hence justifying asthma as an obstructive lung disease.
| Etiology |
|---|
- The etiology of asthma is likely highly complex and involves interactions of predisposing genetic and environmental factors. Whatever the case, the current thought is that asthmatic individuals have an underlying chronic inflammation in their conducting airways that renders the airways hyper-responsive to certain stimuli. In some cases, these stimuli are identifiable external antigens derived from cats, dogs, plants, or rodents, termed "Extrinsic Asthma", whereas in others, termed "Internal Asthma" they are poorly-understood internal stimuli that are released during exercise, exposure to cold, or in response to cryptic viral infections, termed
- Individuals with extrinsic asthma typically display a general predilection to other other types of allergic reactions, display increased serum concentrations of IgE, and may possess a general derangement in their Type I Hypersensitivity response. Those with extrinsic asthma tend to be younger, between 20 - 40 years of age, and may display some family history of asthma. In contrast, intrinsic asthma manifests at a later age with no family history and shows no correlation with IgE levels or other allergies.
| Morphology |
|---|
- Asthma is characterized by characteristic morphological changes to the airway wall from the trachea to the terminal bronchioles, although pathology is the most intense in the bronchi. The respiratory lamina propria displays a characteristic chronic inflammatory infiltrate which includes eosinophils, macrophages, mast cells, and T-cells. The most characteristic inflammatory findings in asthma are the eosinophilic infiltrate and the T-cells which are skewed to the Th2 subtype of CD4+ T-cells and appear to secrete IL-4 and IL-5. In addition to the inflammation, the airways display a thickening of the basement membrane of the respiratory epithelium, hypertrophy of the respiratory smooth muscle layer, and an increased number of respiratory submucosal glands as well as epithelial goblet cells.
- These changes are evident in patients at baseline and may represent the morphological basis of the increased airway hypersensitivity. During an acute ashthmatic attack the respiratory epithelium may undergo necrosis and shed into the lumen while epithelial goblet cells rapidly produce mucous to the point that the airway lumen may become filled with a thick mucinous plug. In addition, the entire airway wall may display hyperemia as well as edema during an acute asthmatic attack.
| Pathogenesis |
|---|
- The pathogenesis of asthmatic attacks appears to follow a biphasic course characterized by early and late phases. The early phase, lasting roughly an hour, appears to be caused by a degranulation of mast cells which release a variety of soluble mediators such as leukotrienes, prostoglandins, and histamine that induce potent bronchoconstriction and hyper-secretion of mucus. The presence of these soluble mediators then initiates the late phase, lasting several hours, that involves the recruitment of inflammatory cells, especially eosinophils which subsequently release soluble factors that damage the airway. The bronchoconstriction and mucous secretion can potently narrow the luminal diameter of conducting airways and in doing so can dramatically increase their airflow resistance. The consequent perturbations in ventilation can cause profound ventilation-perfusion defects that can lead to significant hypoxemia. Importantly, the resistance to airflow and consequent obstructive pattern of pulmonary function is fully reversible in asthma and is rapidly alleviated by bronchidilators.
| Clinical Consequences |
|---|
- Attacks of asthma can are characterized by episodes of wheezing, dyspnea, and coughing that may last up to several hours and are relieved by administration of bronchodilators. If untreated, patients may display significant hypoxemia that can be fatal if the attack is sufficiently severe.