Asthma

Asthma is a disease of the airways characterized by chronic inflammation and abnormally heightened responsiveness of the tracheobronchial tree, leading to reversible expiratory airflow obstruction. A key feature of asthma is its episodic nature: acute exacerbations separated by symptom-free periods.

EPIDEMIOLOGY OF ASTHMA AND SIGNS AND SYMPTOMS

Asthma affects an estimated 4% to 5% of the U.S. pop ulation. Onset is generally among younger patients; about half of cases manifest prior to 10 years of age, and another third before 40 years of age. In childhood, there is a 2:1 male-to-female preponderance, but by 30 years of age, the sexes are equally affected. A documented increase in the prevalence of asthma has occurred in the United States over the past several decades. Numerous theories have been proposed for this increase, but the exact reasons are still unclear. It does not appear that increased awareness of the disease is the reason for the increased prevalence. One theory holds that decreased exposure to childhood infections results in skewing of the immune system toward Th2 responses.
  Death related to asthma is infrequent (approxi mately 1 for 100,000 population), but there are indi cations that the mortality rate has been rising over the past 10 to 15 years. The precise reason for this rise in asthma-related mortality is not known, but it has been suggested it is a reflection of improper man agement of asthma, in particular an overreliance on Beta-agonist bronchodilators.

ETIOLOGY AND PATHOGENESIS OF ASTHMA

Asthmatics have greater degrees of airway reactivity (i.e., bronchoconstriction) to inhaled stimuli such as histamine, methylcholine, and cold air when compared with nonasthmatics. Similarly, asthmatics exhibit heightened response to bronchodilators.
The pathophysiology of this airway hypersensitivity is not entirely clear. However, chronic airway inflam mation appears to have an important role. A number of stimuli can lead to chronic airway inflammation:

  • Inhaled allergens (e.g., animal dander, molds, dust mites)
  • Viral and Mycoplasma infections
  • Low-molecular-weight chemicals (including indus trial dusts and gases)

Inhaled allergens are the most commonly encountered and important causes of chronic airway inflammation. Patients with so-called allergic asthma have increased serum IgE levels and positive skin-test results to air borne antigens. In some patients, chronic inflammatory stimuli cannot be identified, yet they still have severe airway inflammation. These patients are referred to as having intrinsic asthma.

  An acute asthma attack is triggered by stimuli that cause bronchoconstriction:

  • Cold air
  • Exercise
  • Inhaled irritants (cigarette smoke, dust, aerosols such as hairspray or perfume)
  • Beta-adrenergic blockers
  • Emotional upset
  • Nonsteroidal anti-inflammatory drugs
  • Food additives (e.g., sulfites)
  • Inhaled allergens

Given the key role that inflammation appears to play in the pathogenesis of asthma, significant attention has been directed at studying the precise nature of the inflammatory response in the disease. Studies of biopsies

PEF and symptoms occur with initial treatment, ABG measurement is unnecessary.
Chest radiographs are generally unnecessary but typ ically reveal hyperinflation and possibly atelectasis sec ondary to mucous plugging. Chest radiographs can reveal pneumonia as well as complications of a severe attack such as pneumothorax and pneumomedi astinum and should be obtained if such conditions are suspected.

TREATMENT OF ASTHMA

Given the pathophysiology of asthma, prevention of acute attacks depends on limiting the degree of chronic inflammation, whereas treatment of an acute attack involves the relief of bronchoconstriction. The use of anti-inflammatory agents limits acute attacks, and the use of bronchodilators provides symptomatic relief during exacerbations. Patient education is a key aspect of effective management. Patients need to know the basic pathophysiology of asthma and to understand the difference between preventive treatment and sympto matic treatment. Patients need to be taught how to rec ognize exacerbations early and to institute prompt treatment. Control of the patient's environment is another important aspect of asthma management. It is crucial to avoid sensitizing agents such as inhaled allergens and bronchospastic triggers such as nonsteroidal anti-inflammatory agents.

Corticosteroids are the most potent anti-inflammatory agents available. They are generally administered via the inhaled route using a metered-dose inhaler (MDI). For stable patients, inhaled steroids can provide benefits equivalent to ingested steroids with fewer systemic effects. Oral steroids are generally reserved for the treat ment of acute attacks or for maintenance in the rare patient who is not controlled with inhaled steroids alone.
A newer class of anti-inflammatory agents includes drugs that modify the inflammatory mediators known as leukotrienes. Montelukast and zafirlukast are leukotriene receptor antagonists, whereas zileuton inhibits the synthesis of leukotrienes. These drugs are possible alternatives to inhaled corticosteroids in patients with mild asthma or combined with inhaled steroids for patients with more severe disease.

Sodium cromoglycate and nedocromil are two related noncorticosteroid agents that are able to bluntthe effect of inflammatory inducers and certain bron chospastic triggers (especially cold air and exercise). They are particularly effective in patients who have a significant allergic component to their asthma. The precise mechanism of action of the agents is not yet clear.
Beta-Agonists are the most potent and widely used bron chodilators. Generally administered via MDI to limit sys temic side effects (e.g., tachycardia, tremors), they pro vide prompt symptomatic relief, but because they do not have intrinsic anti-inflammatory action, they do not alter the underlying pathophysiology. Inhaled, medi um-acting Beta2-selective agonists (e.g., albuterol, terbu taline, pirbuterol, metaproterenol) are generally used for immediate relief. Long-acting agents (salmeterol) can be used in combination with anti-inflammatory agents for long-term control but generally never on their own.
Theophylline and related methylxanthines have moderate bronchodilatory action but may also improve respiratory muscle function and increase respiratory drive. Administered via the oral route (although some times used intravenously during an acute attack), they can be useful for the prevention of nocturnal symp toms. Serum levels need to be monitored because nau sea, palpitations, and seizures can result from toxic lev els. The advent of more potent topical agents as well as multiple drug interactions has resulted in decreased use of these agents.

Inhaled anticholinergic agents such as ipratropium bromide causes bronchodilation through inhibition of vagal stimulation of the airways. It has a slower onset and usually a lower peak effect in most asth matics when compared with the Beta-agonists. Although ipratropium bromide is the first-choice bronchodilator for use in patients with COPD, only certain asthmatics, particularly older patients with intrinsic asthma, benefit from its routine symptomatic use.
During an acute attack, most asthmatics benefit from supplemental oxygen to maintain oxygen satu ration at 90% or higher. Hypoventilation caused by loss of hypoxic drive is extremely rare in asthma, as opposed to the case in chronic bronchitis.
The National Heart, Lung, and Blood Institute has published guidelines for the classification of asthma, along with recommendations for long-term and symp tomatic therapy. The emphasis is on proper maintenance therapy (with anti-inflammatory medica tion) with minimal reliance on short-acting Beta-agonist agents.