Acute Airway Obstruction
â¢ Â What are the clinical manifestations and common causes of acute Â airway obstruction?
â¢ Â What are the pathogenesis and clinical manifestations for conditions that cause obstruction of the airway lumen?
â¢ Â What is the role of inflammation in the development of asthma?
â¢ Â How does the underlying genetic defect in cystic fibrosis lead to pulmonary and exocrine gland dysfunction?
â¢ Â How does smoking cause both the alveolar destruction of emphysema and the bronchial damage of chronic bronchitis?
â¢ Â What is the rationale for using drugs such as ?2 agonists,acetylcholine antagonists, leukotriene inhibitors, corticosteroids, Â and mast cell stabilizers to manage obstructive pulmonary Â disorders?
Asthma is a lung disease characterized by (a) airway obstruction that is Â reversible (but not completely in some patients), (b) airway inflammation, Â and Â (c) Â increased Â airway Â reactivity Â to Â a Â variety Â of Â stimuli. Â In Â terms Â of Â symptoms, Â asthma Â is Â defined Â by Â paroxysms Â of diffuse Â wheezing, Â dyspnea, Â and Â cough Â resulting Â from Â spasmodic Â contractions Â of Â the Â bronchi. Airway inflammation leads to epithelial denudation, collagen Â deposition beneath the basement membrane, mast cell activation, mucosal edema, increased viscid secretions, and smooth muscle contraction. With Â proper treatment, most patients with asthma can control the disease Â and prevent development of emphysema or bronchitis. Asthma occurs Â in Â about Â 7% Â to 14% Â of Â the Â U.S. population Â and Â is Â common Â amongÂ children and adults, with an annual mortality rate of 10.7 per 1 million Â people, or approximately 3400 people. The annual direct and indirect Â cost Â of Â asthma Â is Â estimated Â at Â more Â than Â $56 Â billion. Asthma is themost common chronic disease of childhood with a disproportionally Â high Â prevalence Â rate Â in African Â Americans, Â inner-city Â dwellers, Â and Â premature or low-birth-weight children. The pathophysiology of both Â intrinsic (nonallergic, sometimes referred to as adult onset) and extrinsic Â (allergic, sometimes referred to as Â pediatric onset) asthma is thought Â to involve inflammation of the airways. Most cases of asthma can be Â triggered both by allergens and by stimuli, such as exercise and exposure Â to Â cold Â air. Â The Â terms Â intrinsic Â and Â extrinsic Â are Â still Â used, Â but Â many Â prefer the terms nonallergic and allergic. The clinical features of all forms Â are similar.
Asthma is associated with the release of inflammatory chemicals from Â mast cells in the airways. The mechanisms stimulating mast cell release are Â immunoglobulin E (IgE)âmediated triggers for extrinsic/allergic asthma Â (Fig. 22.1). Intrinsic/nonallergic asthma occurs in patients who have no Â history of allergy. Allergic asthma (extrinsic) comprises approximately Â one Â third Â to Â one Â half Â of Â all Â cases. Â Asthma Â is Â often Â associated Â with Â a Â history of hay fever or eczema (atopy), a positive family history of the Â disease, and positive skin test reactions to allergens (dust mites, cat/dog Â dander, industrial chemicals). Pharmacologic therapy, allergen-specific Â immunotherapy, Â and Â environmental Â control Â are Â usually Â beneficial. Â Refer to Chapter 10 for details about IgE-mediated mechanisms and Â hyposensitization methods.
Patients with nasal polyps, sinusitis, and asthma, ingestion of aspirin Â may induce severe or occasionally fatal asthmatic attacks. Sometimes anaphylactoid Â reactions Â cause Â a Â decrease Â in Â blood Â pressure, Â itching Â (pruritus), rhinorrhea, or a rash after aspirin ingestion. Aspirin intoler ance with asthma usually occurs in adults. Attacks may occur withinÂ minutes of ingestion or may be delayed up to 12 hours. Nonsteroidal antiinflammatory Â drugs Â such Â as Â indomethacin Â (Indocin), Â ibuprofen Â (Motrin, Â Advil), Â and Â related Â drugs Â may Â also Â induce Â asthma Â in Â the aspirin-intolerant patient. Aspirin reactions are not immunologically Â mediated. Â Therefore Â skin Â testing Â is Â not Â useful Â for Â diagnosing Â aspirinÂ
intolerance. Because aspirin and nonsteroidal antiinflammatory drugs Â inhibit the conversion of arachidonic acid to prostaglandins, it is possible Â that Â aspirin Â shunts Â arachidonic Â acid Â breakdown Â products Â to Â the Â leukotriene Â system. Â Leukotrienes, Â released Â from Â mast Â cells, Â are Â slow- reacting substances of anaphylaxis with powerful bronchoconstrictionÂ activity (see Fig. 22.1). Avoidance is the most practical approach to this problem because testing can be dangerous. Asthma can occur from ingestion of food additives. Tartrazine (yellow Â dye no. 5), which is used to color pharmaceuticals, hair products, and Â food products, may also produce severe asthma in susceptible persons.Â A Â complete Â list Â of Â drugs containing Â tartrazine Â can Â be Â obtained Â from Â the Food and Drug Administration. Monosodium Â glutamate, Â used Â as Â a Â flavor Â enhancer Â in foods, Â can Â produce Â faintness, Â nausea, Â sweating, Â a Â fall Â in Â blood Â pressure, Â and, Â occasionally, asthma. Sodium or potassium metabisulfite, used to preserveÂ fruits, Â vegetables, Â and Â meats, Â can Â cause Â anaphylactoid Â reactions. Â A Â challenge with the chemical may be necessary to establish a diagnosis, Â as metabisulfites are widespread in our society. Hops in beer have also been implicated in causing severe broncho- spasm. Skin reactivity does not occur, and the mechanism of the problemÂ is not IgE mediated. The diagnosis involves a history of exposure followed Â by symptoms. Gastroesophageal reflux disease can trigger an asthma attack. It is assumed that the gastric acid reflux in the esophagus is aspirated into Â the lungs, resulting in bronchoconstriction.