Clinical Manifestations and Causes of Airway Obstruction, Pathogenesis of Asthma and Obstructive Pul

Acute Airway Obstruction

•  What are the clinical manifestations and common causes of acute  airway obstruction?

•  What are the pathogenesis and clinical manifestations for conditions that cause obstruction of the airway lumen?

•  What is the role of inflammation in the development of asthma?

•  How does the underlying genetic defect in cystic fibrosis lead to pulmonary and exocrine gland dysfunction?

•  How does smoking cause both the alveolar destruction of emphysema and the bronchial damage of chronic bronchitis?

•  What is the rationale for using drugs such as ?2 agonists,acetylcholine antagonists, leukotriene inhibitors, corticosteroids,  and mast cell stabilizers to manage obstructive pulmonary  disorders?

Asthma

Asthma is a lung disease characterized by (a) airway obstruction that is  reversible (but not completely in some patients), (b) airway inflammation,  and  (c)  increased  airway  reactivity  to  a  variety  of  stimuli.  In  terms  of  symptoms,  asthma  is  defined  by  paroxysms  of diffuse  wheezing,  dyspnea,  and  cough  resulting  from  spasmodic  contractions  of  the  bronchi. Airway inflammation leads to epithelial denudation, collagen  deposition beneath the basement membrane, mast cell activation, mucosal edema, increased viscid secretions, and smooth muscle contraction. With  proper treatment, most patients with asthma can control the disease  and prevent development of emphysema or bronchitis. Asthma occurs  in  about  7%  to 14%  of  the  U.S. population  and  is  common  among  children and adults, with an annual mortality rate of 10.7 per 1 million  people, or approximately 3400 people. The annual direct and indirect  cost  of  asthma  is  estimated  at  more  than  $56  billion. Asthma is themost common chronic disease of childhood with a disproportionally  high  prevalence  rate  in African  Americans,  inner-city  dwellers,  and  premature or low-birth-weight children. The pathophysiology of both  intrinsic (nonallergic, sometimes referred to as adult onset) and extrinsic  (allergic, sometimes referred to as  pediatric onset) asthma is thought  to involve inflammation of the airways. Most cases of asthma can be  triggered both by allergens and by stimuli, such as exercise and exposure  to  cold  air.  The  terms  intrinsic  and  extrinsic  are  still  used,  but  many  prefer the terms nonallergic and allergic. The clinical features of all forms  are similar.

Asthma is associated with the release of inflammatory chemicals from  mast cells in the airways. The mechanisms stimulating mast cell release are  immunoglobulin E (IgE)–mediated triggers for extrinsic/allergic asthma  (Fig. 22.1). Intrinsic/nonallergic asthma occurs in patients who have no  history of allergy. Allergic asthma (extrinsic) comprises approximately  one  third  to  one  half  of  all  cases.  Asthma  is  often  associated  with  a  history of hay fever or eczema (atopy), a positive family history of the  disease, and positive skin test reactions to allergens (dust mites, cat/dog  dander, industrial chemicals). Pharmacologic therapy, allergen-specific  immunotherapy,  and  environmental  control  are  usually  beneficial.  Refer to Chapter 10 for details about IgE-mediated mechanisms and  hyposensitization methods.

Respiratory Function

Patients with nasal polyps, sinusitis, and asthma, ingestion of aspirin  may induce severe or occasionally fatal asthmatic attacks. Sometimes anaphylactoid  reactions  cause  a  decrease  in  blood  pressure,  itching  (pruritus), rhinorrhea, or a rash after aspirin ingestion. Aspirin intoler ance with asthma usually occurs in adults. Attacks may occur within  minutes of ingestion or may be delayed up to 12 hours. Nonsteroidal antiinflammatory  drugs  such  as  indomethacin  (Indocin),  ibuprofen  (Motrin,  Advil),  and  related  drugs  may  also  induce  asthma  in  the aspirin-intolerant patient. Aspirin reactions are not immunologically  mediated.  Therefore  skin  testing  is  not  useful  for  diagnosing  aspirin 
intolerance. Because aspirin and nonsteroidal antiinflammatory drugs  inhibit the conversion of arachidonic acid to prostaglandins, it is possible  that  aspirin  shunts  arachidonic  acid  breakdown  products  to  the  leukotriene  system.  Leukotrienes,  released  from  mast  cells,  are  slow- reacting substances of anaphylaxis with powerful bronchoconstriction  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  dye no. 5), which is used to color pharmaceuticals, hair products, and  food products, may also produce severe asthma in susceptible persons.  A  complete  list  of  drugs containing  tartrazine  can  be  obtained  from  the Food and Drug Administration. Monosodium  glutamate,  used  as  a  flavor  enhancer  in foods,  can  produce  faintness,  nausea,  sweating,  a  fall  in  blood  pressure,  and,  occasionally, asthma. Sodium or potassium metabisulfite, used to preserve  fruits,  vegetables,  and  meats,  can  cause  anaphylactoid  reactions.  A  challenge with the chemical may be necessary to establish a diagnosis,  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 problem  is not IgE mediated. The diagnosis involves a history of exposure followed  by symptoms. Gastroesophageal reflux disease can trigger an asthma attack. It is assumed that the gastric acid reflux in the esophagus is aspirated into  the lungs, resulting in bronchoconstriction.