Wilber is a five-year-old male child of two upper-middle-class parents who live in Spotless Dell Community in a recently built home. Wilber has previously been healthy with only an occasional upper respiratory tract infection. About a month ago, Wilber complained of facial pain along with a case of the “sniffles.” He began to cough at night (generally in the early a.m.) and also when he played outside with other children. Because the coughing was mild and tended to stop on its own and was not accompanied by production of sputum (was “nonproductive”), Wilber’s parents were not concerned and assumed he had a “cold.” About two weeks ago, Wilber’s parents purchased a robotic vacuum cleaner (a Roomba™ ). Wilber enjoyed following it around his bedroom but started to complain about feeling “funny” in his chest. His mother noticed that he made an odd “whistling” sound as he breathed out (expired). Wilber’s complaints were occasional but tended to occur when the vacuum cleaner was being used or when Wilber’s mother fluffed up the duvet or changed the sheets on Wilber’s bed. Concerned that Wilber might be developing an “allergy,” his parents brought Wilber to see his pediatrician. Wilber’s pediatrician was concerned that the child’s symptoms might indicate very mild pediatric asthma. Wilber did report some facial pain when pressure is applied to his maxillary area, and the pediatrician noted that his conjunctiva were slightly inflamed, suggesting the possibility of mild allergic rhinitis. His physical examination was otherwise normal. Still concerned, the pediatrician asks Wilber to imagine he is trying to “blow out birthday candles as hard as possible.” With forced expiration, she notices a distinct wheeze (whistling sound due to air turbulence on expiration, suggesting some degree of pulmonary obstruction). Because the symptoms are mild, the pediatrician elects to forgo additional testing and suggests that Wilber’s parents should not use the vacuum cleaner in Wilber’s presence and that they buy special impermeable bed covers for his room. The pediatrician also prescribes a rapid acting beta-2 agonist as an inhaler (albuterol). The drug causes smooth muscle relaxation in the respiratory system, acting as a bronchodilator. The pediatrician instructs Wilber’s parents to use the drug when episodes of wheezing occur. His parents are also instructed to keep track of how frequently wheezing occurs and to immediately report back if symptoms worsen or if the wheezing is not relieved. The medication initially controls Wilber’s wheezing attacks, but after a time they appear to increase in frequency. Wilber complains of increased chest discomfort and interacts less with his playmates. Wilber’s pediatrician is now more concerned about the presence of asthma and prescribes the use of an inhaled corticosteroid (beclomethasone), which both acts as an inhibitor of and relaxer for bronchoconstriction and as an anti-inflammatory reducing the sensitivity of the airway to agents inducing the asthma attacks. She instructs the parents to use the albuterol inhaler only when Wilber suffers from sudden discomfort. Wilber does much better on the inhaled corticosteroid for several months, and his parents decide to taper the medication, noting no change in Wilber’s health. Wilber and his parents decide to visit his grandparents who live in a 120-year-old house on a ranch in Dusty Gulch. Wilber’s parents pack the albuterol inhaler because they are somewhat concerned about the presence of “dust and germs” triggering an attack. At his grandparents’ house, Wilber sleeps in a room with heavy hand-woven carpets on the floor and antique loomed fabrics on the walls. He wakes up in the early morning and calls his parents, complaining of difficulty breathing. He says his chest feels tight, and his parents note a very loud wheeze as Wilber attempts to exhale. They note that his chest muscles seem to be “working hard” as he attempts to breath. They have Wilber use the albuterol inhaler, but it has little effect. Panicked, they rush Wilber to the local hospital’s urgent care center. At the center the on-call resident notes that Wilber has a very increased respiratory rate (over 30 breaths per minute), an increased heart rate (130 beats per minute), and a markedly reduced oxyhemoglobin saturation (determined using a pulse oxymeter to be 92 percent saturation). Concerned with the inability of a moderate dose of a rapid acting brochodilator to afford relief, the resident increases the dose of this drug and begins IV therapy with corticosteroids. He also has Wilber inhale oxygen via a face mask. After an hour, Wilber’s oxyhemoglobin saturation begins to climb, and after six hours Wilber is feeling much better with improved breathing and lack of wheezing. He is scheduled for an intensive workup by a pediatric allergist in the next few days.
Discussion Asthma is a complex chronic disease in which symptoms result from an obstruction of air flow, which is often periodic and triggered by an inciting agent. The most common inciting agent is an environmental allergen that triggers immune-mediated brochospasm, mucosal edema, and excess mucous production, which plug the airways. With time this leads to structural changes in the airway that include the continued presence of inflammatory cells (often eosinophils), basement membrane thickening, mucous gland hyperplasia, and mucoid plugging of airways (FIGURE 15-25). The immunopathology of asthma is complex and is discussed in the presentation on immunology, hypersensitivity, allergy, and autoimmune diseases. In brief, IgE antibodies reactive with the allergen bind to mast cells in the respiratory tree. In the presence of allergen, the IgE antibodies trigger the mast cells to immediately release a number of inflammatory mediators (including histamine, prostaglandins, and leukotrienes) that mediate bronchoconstriction. With time the activated mast cells also will release additional mediators that promote the migration of numerous inflammatory cells into the tissues of the airway, notably eosinophils. These cells promote additional airway damage. Many environmental allergens can trigger allergic asthma. At the top of the list are dust mites, other household insects such as roaches, and animal dander. The hygiene hypothesis suggests that current increases in the rate of childhood asthma are a result of child rearing in an excessively clean environment. Studies have suggested that children raised in farm environments have fewer cases of asthma than those raised in nonrural environments. In Wilber’s case, the association of symptoms with exposure to vacuuming, disturbed bedding, and textiles suggests that household dust mites are a likely trigger. The treatment of asthma is complex and far more extensive than discussed in the Case. Treatment involves pulmonary function tests, determination of the allergic trigger, and evaluation of multiple potential therapeutic interventions. However, it is important to understand that asthma is a serious disease affecting at least 10 percent of the population. There has been a surprising increase in incidence (some accounts report increases of over 75 percent in recent years). Asthma is the most common reason for admission to pediatric hospitals and accounts for more school absences than any other chronic disease. In addition, unrelieved asthma (status asthmaticus) results in 5,000 deaths per year. Figure 15-25 is taken from such a lethal case.
FIGURE 15-25
Etiology and Pathogenesis Allergic asthma triggered by the presence of environmental allergens, possibly dust mites, resulting in inflammation of the respiratory tree, airway hypersensitivity, bronchospasm, excess mucous production, and inflammation-induced changes in the respiratory tree.
Questions
1. In addition to dust mites, insects, and animal dander, what are other common triggers for allergic asthma?
2. What are common nonallergic triggers for asthma?
3. Can you think of any additional studies that would help to prove (or disprove) the hygiene hypothesis of asthma susceptibility?
4. Allergic asthma is an example of type 1 hypersensitivity. What are the major characteristics of this type of hypersensitivity reaction?
5. How could Wilber’s parents alter their household environment to prevent additional asthmatic attacks in Wilber?
6. How can the allergen(s) responsible be identified?