Porth's Essentials of Pathophysiology, 4e

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Disorders of Ventilation and Gas Exchange

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long-term treatment of asthma. Inhaled corticosteroids administered by MDI usually are preferred because of minimal systemic absorption and reduced disruption in hypothalamic-pituitary-adrenal function. The long-acting β 2 -agonists, available for administra- tion by the inhaled or oral routes, act by relaxing bron- chial smooth muscle. They are used as an adjunct to anti-inflammatory medications for providing long-term control of symptoms, especially nocturnal symptoms, and for preventing exercise-induced bronchospasm. The long-acting β 2 -agonists have durations of action of at least 12 hours and should not be used to treat acute symptoms or exacerbations. 19 The leukotriene receptor antagonists (monelukast and zafirlukast) block the action of the leukotrienes, which are arachidonic acid derivatives synthesized by a number of inflammatory cells in the airways, including eosinophils, mast cells, macrophages, and basophils. 19,31 Several of the leukotrienes exert many of the effects known to occur in asthma, including bronchoconstriction, increased bron- chial reactivity, mucosal edema, and mucus hypersecre- tion. A particular advantage of the leukotriene receptor antagonists is that they are taken orally. Theophylline, a phosphodiesterase inhibitor, is a bronchodilator that acts by relaxing bronchial smooth muscle. The sustained-release form of the drug is used as an adjuvant therapy, particularly to relieve nighttime symptoms. 19 It may be used as an alternative, but not preferred, medication in long-term preventative therapy when there are issues concerning adherence with regi- mens using inhaled medications or when cost is a factor. Because elimination of the drug varies widely among persons, blood levels are required to ensure that a thera- peutic but not toxic dose is achieved. 17 The anti-IgE monoclonal antibody omalizumab is the first biologic immunoregulatory agent available to treat asthma. 29 It binds to the portion of the IgE that recog- nizes its receptor on the surface of mast cells and baso- phils. Omalizumab, which is indicated for treatment of moderate and severe persistent asthma, is administered subcutaneously every 2 to 4 weeks, depending on the dose. The drug has been approved for adults and chil- dren 12 years of age and older. Severe Asthma Severe (or refractory) asthma represents a subgroup (probably <10%) of persons with asthma who have high medication requirements to maintain good symptom con- trol, or who continue to have persistent symptoms despite high medication use. 32,33 The condition has been described as persistent asthma that required continuous high-dose inhaled or oral corticosteroids for more than 50% of the previous year and the need for additional daily treatment with controller medications, exhibited evidence of disease exacerbations or instability, and required hospitalizations or emergency room visits. 19,21,32,33 Persons with severe asthma are at increased risk for a fatal or near-fatal asth- matic attack. Underestimating the severity of the attack may be a contributing factor. 34 Deterioration often occurs rapidly during an acute attack, and underestimation of

its severity may lead to a life-threatening delay in seeking medical attention. Little is known about the causes of severe asthma. Among the proposed risk factors are genetic predisposi- tion, continued allergen or tobacco exposure, infection, intercurrent sinusitis or gastroesophageal reflux disease, and lack of compliance or adherence with treatment mea- sures. 33 Because bronchial asthma likely involves multiple genes, mutations in genes regulating cytokines (e.g., IL-4), growth factors, or receptors for medications used in treat- ment of asthma ( β 2 -adrenergic agonist or glucocorticoid) could be involved. Environmental factors include both allergen and tobacco exposure, with the strongest reac- tion occurring in response to house dust mite antigens, cockroach allergen, and Alternaria exposure. Bronchial Asthma in Children Asthma is a common chronic illness in children. In the United States, asthma is the most common cause of childhood emergency department visits, hospitaliza- tions, and missed school days. 35–38 Although childhood asthma may have its onset at any age, up to 80% of children who develop asthma are symptomatic before 5 years of age. 19 Asthma is more prevalent among black than white children. 36–39 Worldwide, childhood asthma appears to be increasing in prevalence. 35 It is particularly common in children living in suburban areas, as com- pared to rural areas of developing countries. As with adults, asthma in children commonly is asso- ciated with an IgE-related reaction. It has been suggested that IgE directed against respiratory viruses in particular may be important in the pathogenesis of wheezing ill- nesses in infants (i.e., bronchiolitis), which often precede the onset of asthma. 37,38 Previous severe infections with the respiratory syncytial virus (RSV) are a risk factor in the development of asthma. Other contributing fac- tors include exposure to environmental allergens such as pet dander, dust mite antigens, and cockroach allergens. Exposure to environmental tobacco smoke also contrib- utes to asthma in children. 36–39 The signs and symptoms of asthma in infants and small children vary with the stage and severity of an attack. Because airway patency decreases at night, many children have acute signs of asthma at this time. Often, previously well infants and children develop what may seem to be a cold with rhinorrhea, rapidly followed by irritability, nonproductive cough, wheezing, tachypnea, dyspnea with prolonged expiration, and use of acces- sory muscles of respiration. Cyanosis, hyperinflation of the chest, and tachycardia indicate increasing severity of the attack. Wheezing may be absent in children with extreme respiratory distress. The symptoms may prog- ress rapidly and require a trip to the emergency depart- ment or hospitalization. As with adults and older children, the Expert Panel of the NAEPP recommends a stepwise approach to diag- nosing and managing childhood asthma. 19 Treatment involves not only pharmacologic agents but also