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A 10-year-old girl with a history of poorly controlled asthma presents to the emergency department with severe shortness of breath and audible inspiratory and expiratory wheezing. She is pale, refuses to lie down, and appears extremely frightened. Her pulse is 120 bpm and respirations 32/min. Her mother states that the girl has just recovered from a mild case of flu and had seemed comfortable until this afternoon. The girl uses an inhaler (albuterol) but "only when really needed" because her parents are afraid that she will become too dependent on medication. She administered two puffs from her inhaler just before coming to the hospital, but "the inhaler doesn't seem to have helped." What emergency measures are indicated? How should her long-term management be altered?

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Asthma is characterized clinically by recurrent bouts of shortness of breath, chest tightness, and wheezing, often associated with coughing; physiologically by widespread, reversible narrowing of the bronchial airways and a marked increase in bronchial responsiveness to inhaled stimuli; and pathologically by lymphocytic, eosinophilic inflammation of the bronchial mucosa. It is also characterized pathologically by "remodeling" of the bronchial mucosa, with thickening of the lamina reticularis beneath the airway epithelium and hyperplasia of the cells of all structural elements of the airway wall—vessels, smooth muscle, and secretory glands and goblet cells.

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In mild asthma, symptoms occur only occasionally, as on exposure to allergens or certain pollutants, on exercise, or after viral upper respiratory infection. More severe forms of asthma are associated with frequent attacks of wheezing dyspnea, especially at night, or with chronic airway narrowing, causing chronic respiratory impairment. These consequences of asthma are regarded as largely preventable, because effective treatments for relief of acute bronchoconstriction ("short-term relievers") and for reduction in symptoms and prevention of attacks ("long-term controllers") are available. The persistence of high medical costs for asthma care, driven largely by the costs of emergency department or hospital treatment of asthma exacerbations, are believed to reflect underutilization of the treatments available.

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The causes of airway narrowing in acute asthmatic attacks, or "asthma exacerbations," include contraction of airway smooth muscle, inspissation of viscid mucus plugs in the airway lumen, and thickening of the bronchial mucosa from edema, cellular infiltration, and hyperplasia of secretory, vascular, and smooth muscle cells. Of these causes of airway obstruction, contraction of smooth muscle is most easily reversed by current therapy; reversal of the edema and cellular infiltration requires sustained treatment with anti-inflammatory agents.

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Short-term relief is thus most effectively achieved by agents that relax airway smooth muscle, of which β-adrenoceptor stimulants (see Chapter 9) are the most effective and most widely used. Theophylline, a methylxanthine drug, and antimuscarinic agents (see Chapter 8) are sometimes also used for reversal of airway constriction.

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Long-term control is most effectively achieved with an anti-inflammatory agent such as an inhaled corticosteroid. It can also be achieved, though less effectively, with a leukotriene pathway antagonist or ...

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