ANSWERS Board Review Quiz – February 2010 ALLERGY AND RELATED DISORDERS AND RESPIRATORY DISORDERS 1. Question 175 (2009) ANSWER: D – oral candidiasis Despite remaining the cornerstone therapy for persistent asthma, many parents are reluctant to have their children begin using inhaled corticosteroids. Addressing parents' concerns and outlining the potential adverse effects may improve understanding and compliance. Local oropharyngeal symptoms, including dysphonia, oral candidiasis, and cough, are commonly encountered adverse effects of inhaled corticosteroids. Local symptoms appear to be dose-related and can be lessened by using a "spacer" and rinsing out the mouth after use. A number of studies have documented a transient decrease in growth velocity during the first year of inhaled corticosteroid therapy, but a daily cumulative dose up to 800 mcg of inhaled budesonide has been shown not to affect predicted adult height. Less common adverse effects of inhaled steroids include acne, mood swings, weight gain, decreased serum immunoglobulin G concentrations, and rarely, posterior subcapsular cataracts and adrenal suppression. Inhaled steroids are used in persistent asthma to help halt lung remodeling by decreasing bronchial inflammation, reducing inflammatory mediators, and decreasing bronchial hyperresponsiveness. 2. Question 114 (2009) ANSWER: B – laryngomalacia The infant described in the vignette has congenital stridor (noisy inspiratory breathing) and exhibits only mild increased work of breathing when supine and when distressed. Although no immediate intervention is required to maintain airway patency, the clinician examining the patient needs to determine the cause of the stridor. Some have reported a characteristic coarseness of the stridor when due to a supraglottic (laryngeal) disorder, a musical quality associated with glottic (vocal cord) disorders, and more of an expiratory noise or prolonged expiratory phase with a wheeze in subglottic disorders of airway obstruction (Item C114A). The most common cause of congenital stridor is laryngomalacia, a congenital weakness, or floppiness, in airway laryngeal cartilages (epiglottis, arytenoid cartilages, larynx) (Item C114B). A cleft lip does not cause stridor. A tracheal hemangioma (Item C114C) may cause airway obstruction, but usually this is associated with expiratory wheezing. Tracheomalacia may complicate prolonged intubation and positive pressure ventilation in preterm infants and typically is associated with expiratory wheezing or inspiratory cessation of airflow with airway collapse unless positive distending pressure is applied (Item C114D). A vocal cord polyp is a rare congenital condition that may be associated with human papillomavirus infection that can cause stridor, which would not be expected to change with position. 3. Question 207 (2009) ANSWER: E – vocal cord dysfunction The teenager described in the vignette has signs and symptoms consistent with vocal cord dysfunction (VCD), a condition that can mimic or coexist with asthma. In contrast to an asthma exacerbation, the key features of VCD exhibited by this girl include a normal room air pulse oximetry reading, failure to improve with her beta2 agonist inhaler, clear lungs, and difficulty with inspiration instead of expiration. A blunted inspiratory loop on spirometry also is supportive of VCD, although affected patients usually have normal spirometry readings when not experiencing symptoms. Triggers for VCD can include viral upper respiratory tract infections, chemicals, fumes, pollution, emotional changes, laughing, exercise, gastroesophageal reflux (GER), and cold air. GER can cause cough and be a trigger for asthma. It may worsen during exercise, eating, or when supine. Although GER is a cause of chronic cough, the patient in the vignette does not admit to GER symptoms, making this diagnosis unlikely. Postnasal drip syndrome, now termed upper airway cough syndrome, can result in coughing due to allergic rhinitis, nonallergic rhinitis, or sinusitis. The lack of nasal congestion, rhinorrhea, or postnasal drip for this girl makes this an unlikely cause of her acute symptoms. Psychogenic cough, also called habit cough syndrome, is a well-described chronic cough that may begin after a viral upper respiratory tract infection. The cough usually is nonproductive and does not occur during sleep. Teenagers who have asthma may use coughing as a method to avoid school (factitious or malingering), but the girl in the vignette is not having symptoms during a specific class or time of day. 4. Question 111 ANSWER: B – most cases are preceded by an upper respiratory tract infection Psychogenic cough, sometimes called habit-cough syndrome, is an uncommon cause of chronic cough in children and adolescents. Many experts discourage using the label "psychogenic" because underlying psychological or psychosomatic concerns are uncommon in affected children. Most cases of psychogenic cough begin with an uncomplicated upper respiratory tract viral illness, but the cough lingers for months to years. The classic triad of symptoms includes a repetitive cough, cessation during sleep, and the characteristic hacking, barky cough, as described for the boy in the vignette. Although most affected children undergo multiple therapeutic interventions and diagnostic tests, the characteristic presentation may allow clinicians to avoid expensive or invasive tests to rule out other causes. Successful therapies for habit-cough include behavioral therapy, suggestion therapy, and self- hypnosis. Once resolved, most cases of habit-cough do not recur. Unlike some cases of viral upper respiratory tract infections, habit-cough resolution is not followed by recurrent wheezing. 5. Question 15 (2010) ANSWER: E – her son’s symptoms are related to his allergic rhinitis The boy described in the vignette is exhibiting a common form of food allergy called food pollen syndrome or oral allergy syndrome (OAS). OAS is seen in 30% to 40% of children who have allergic rhinitis. Certain foods contain proteins that are similar to airborne allergens, and patients who are allergic to an aeroallergen are at risk of developing reactions to the cross-reacting food protein (Item C15). In most cases, symptoms are isolated to the oropharynx, where food comes in contact with a mucosal surface, and include lip, tongue, and oral mucosal pruritus; tingling; and occasionally angioedema. Interestingly, because these food proteins are heat-labile, cooking the food (eg, apple pie) negates its antigenic properties. Although symptoms typically are mild, there are reports of severe reactions. In one recent review involving 1,361 patients who had OAS, 8.7% experienced systemic symptoms outside the gastrointestinal tract, 3% experienced symptoms other than oral symptoms, and 1.7% experienced anaphylactic shock. Because OAS is relatively specific to particular cross-reacting food(s), patients do not need to avoid other fruits or vegetables to which they have not experienced reactions. Avoidance of unrelated foods (eg, milk, eggs) is not recommended unless the history suggests a previous reaction. The decision to avoid causative foods can be based on the severity of reaction. Referral to an allergist typically is reserved for situations when skin testing is desired or if the child has experienced systemic symptoms. Skin testing is performed using a commercial extract or the fresh fruit or vegetable. When using fresh food, the sensitivity of skin testing with a history of reproducible reactions is close to 90%, while the negative predictive value is more than 90%. The skin prick device is pressed into the food and then pressed in the skin (so-called "prick-prick" skin test). Other immunoglobulin (Ig) E food reactions include atopic dermatitis, eosinophilic esophagitis, and specific food allergy. In the United States, 85% of specific food allergies are due to egg, milk, wheat, soy, peanuts, tree nuts, fish, and shellfish. Most children who have IgE food allergies react to only one or two causative foods, although children who have tree nut allergy, atopic dermatitis, and eosinophilic esophagitis often have IgE-mediated reactions to multiple foods. 6. Question 31 (2010) ANSWER: A – allergy skin testing Clinicians should be aware that many unconventional and unproven testing methods are still promoted for the diagnosis and management of allergic conditions. For example, applied kinesiology theorizes that an allergen or irritant substance provokes weakness when the person ingests, holds, or even stands in close proximity to the offending agent. To date, no conclusive evidence supports this theory or test. The cytotoxic test is an in vitro test involving microscopic evaluation of blood after placing a drop of the offending agent (eg, food, mold) on a slide containing the patient's blood. Changes in the appearance, size, shape, and integrity of leukocytes are interpreted as a "positive" response. A thorough United States Food and Drug Administration review has concluded that the efficacy of the cytotoxic test is unproven. The pulse test evaluates whether an increase or decrease in pulse rate follows food ingestion, injection, or sublingual application and is interpreted as an "allergy" if a change occurs. Finally, provocation-neutralization is a nonstandardized test for food and inhalant allergies. A series of dilutions of an allergen are injected in the upper arm until the patient reports subjective sensations. A progressive series of lower concentrations subsequently are administered until the sensation abates. The lower dose is used for injection treatment to build immunologic tolerance for the offending trigger. Both the testing and treatment method are unproven and should be considered similar to placebo therapy. Finally, Candida immunotherapy or avoidance of yeast ingestion for patients diagnosed with yeast or Candida hypersensitivity is unproven. The parent in the vignette is concerned for mold allergy. Molds generally are believed to have three effects: direct infection through ingestion or inhalation, release of toxins or irritants as mold byproducts, and an immune response (eg, allergic bronchopulmonary aspergillosis, allergic fungal sinusitis, allergic rhinitis, asthma). Significant water damage, leaking water sources, or visible mold growth represent real health concerns. Commercial testing for mold can provide some information, but quantifiable amounts are found in 80% of homes in the United States. Thus, the presence of mold does not necessarily indicate causation. For example, Alternaria alternata is linked to fatal asthma but is primarily an outdoor aeroallergen. Allergy skin prick testing or blood testing can aid in detecting immunoglobulin E-mediated responses to molds and other allergens and is reasonable as part of determining the cause of this adolescent's asthma exacerbations. 7. Question 63 (2010) ANSWER: D – immediately administer 0.3 mg of self-injectable ephinephrine The boy described in the vignette experienced an anaphylactic reaction, a potentially life- threatening event. In children, the most commonly identified causes for anaphylaxis are food, insects, drugs, latex, and vaccines. Food allergy is the most common cause of anaphylaxis in the home or school setting and accounts for an estimated 50% of all pediatric cases annually. Some 85% to 90% of allergic reactions to food in children are due to milk, egg, soy, wheat, peanuts, tree nuts, fish, and shellfish. Peanuts and tree nuts account for most cases of fatal anaphylaxis from foods in the United States. Recently, a panel of experts published a set of clinical criteria for diagnosing anaphylaxis (Item C63). The skin and respiratory system are the most commonly affected systems in cases of food allergy- induced anaphylaxis, as described for the boy in the vignette. Fatal anaphylaxis almost always is due to airway edema and subsequent respiratory failure. For a person experiencing anaphylaxis, epinephrine should be administered immediately and without delay. Observation of the child while calling his parents wastes precious time in this situation. In the school setting, self-injectable intramuscular epinephrine is used. Other methods of delivery, used primarily in the hospital setting, include intravenous, intraosseous, and via an endotracheal tube. Current epinephrine injectors are available in two strengths: 0.15 mg and 0.30 mg. The child in the vignette, who weighs more than 30 kg, should be given the 0.30-mg dose, preferably in the lateral thigh. Antihistamines may decrease pruritus or flushing, but their effect has a slow onset, and they are not recommended as the initial treatment for anaphylaxis. Because some children may require additional doses of epinephrine and observation, emergency services should be called, but waiting for them to arrive to make a decision regarding the initial dose of epinephrine is not recommended. Caregivers of children who have experienced food-induced anaphylaxis should have epinephrine readily available, understand the indications for its use, have a written action plan, and understand the proper technique for use of self-injectable epinephrine devices. 8. Question 143 (2010) ANSWER: E - symptoms can start within 5 minutes of exercise, but peak symptoms usually occur after the exercise is stopped Exercised-induced asthma (EIA) results in a transient narrowing of the airway following vigorous exercise and is associated with a 10% to 15% decrease in the forced expiratory volume in 1 second (FEV1). A number of mechanisms are postulated for EIA, but the most accepted one is based on the decreased warming and humidification of inhaled air during exercise. Upon completion of exercise, there is a marked influx of fluid due to rapid rewarming, which results in mucus production and airway narrowing. Because temperature change is a key aspect of EIA, exercise or sports in cold weather provokes EIA more readily than in warmer weather. Also, a slow warm-up, particularly in cold weather, results in a more gradual change in airway temperature and can lessen EIA symptoms. EIA symptoms such as cough, shortness of breath, and wheezing may begin during exercise but classically peak 5 to 10 minutes after completion of exercise. The more strenuous the exercise, the more intense the asthma attack. For example, running produces more severe airflow limitation than jogging, which, in turn, produces more limitation that walking. Short, intense bouts of work lasting fewer than 2 minutes produce fewer problems than longer periods of effort because of the shortened time of airway cooling. EIA symptoms usually resolve spontaneously after 30 minutes of rest. Exercise is a very common asthma trigger for children, with 70% to 90% of children who have asthma demonstrating EIA symptoms. Pretreatment with a short-acting beta2 agonist is appropriate for isolated EIA. Because most patients who have EIA will be identified with persistent asthma, the latest Global Initiative for Asthma guidelines, published in late 2008, continue to recommend treatment with inhaled corticosteroids to control any underlying persistent asthma. Finally, acute episodes can be attenuated by having the athlete warm up before strenuous exercise. Clinically, exercise challenges usually are performed if the diagnosis of EIA is in doubt or if the patient is not responding appropriately to usual EIA therapies such as beta2 agonists, inhaled corticosteroids, or leukotriene antagonists. Prior to exercise, two baseline spirometry measurements are performed. Ideally, the FEV1 measurements should not differ by more than 3%. The patient then exercises, preferably for the same duration and in the same conditions (eg, running outside on a cold day) that have provoked symptoms previously. Postexercise spirometry is performed at 5, 10, 15, and 30 minutes after exercise. During this challenge, a decrease of 15% in FEV1 is considered consistent with EIA. Other protocols available in a monitored setting include eucapnic voluntary hyperpnea, hypertonic saline challenge, and inhaled powder mannitol challenge. These require a 10% drop in FEV1 to be consistent with EIA. Other conditions that may result in poor exercise performance include vocal cord dysfunction, poor physical conditioning (ie, overweight, out of shape), gastrointestinal reflux, poor cardiac function, and restrictive lung disease. 9. Question 175 (2010) ANSWER: B – formoterol Exercise-induced asthma (EIA) is not only a problem for children and adolescents who have underlying persistent asthma but also can affect 10% to 50% of elite athletes. In addition to ensuring control for underlying persistent asthma, a warm-up period prior to maximal exertion as well as administration of an inhaled beta2 agonist are recommended to prevent EIA. Short-acting beta2 agonists, such as albuterol or levalbuterol, are the most common bronchodilators used. Typically administered 20 minutes prior to activity, short-acting beta2 agonists provide 2 to 4 hours of bronchodilation. However, such treatment may not be effective when anticipated activity is longer, such as the 8 to 12 hours described for the boy in the vignette. Long-acting beta2 agonists that are approved for prevention of EIA in children older than 4 and 5 years of age include salmeterol and formoterol, respectively. However, these agents should not be used as monotherapy for persistent asthma. Formoterol has a faster onset of action than salmeterol (10 minutes versus 30 minutes to reach an increase of 15% in forced expiratory volume in 1 second, and is appropriate for the boy in the vignette. In December 2008, the Pulmonary-Allergy Drugs Advisory Committee recommended that the United States Food and Drug Administration (FDA) consider a ban on the use of both salmeterol and formoterol in children and adolescents. However, the Committee focused on the use of long-acting beta2 agonists for persistent asthma, citing a meta-analysis in adults showing increased risk for asthma-related hospitalization, asthma-related intubation, and asthma-related deaths. At the time of this writing (March 2009), the FDA has not rendered a decision on this issue. Leukotriene receptor antagonists (LTRAs) such as montelukast can be used for EIA. Studies have demonstrated that LTRAs reduce the immediate and late phase of exercise bronchoconstriction. Interestingly, the response to LTRAs varies from poor to excellent. Pharmacogenetic studies are ongoing to determine which patient group exhibits the best response. Anticholinergic inhalers such as ipratropium are not recommended for the treatment of EIA. 10. Question 191 (2010) ANSWER: D - this patient should be tested to all flying hymenoptera (ie, wasps, hornets, bees, yellow jackets) The boy described in the vignette experienced a near-fatal reaction to a flying insect, with signs and symptoms consistent with anaphylaxis. In the United States, stinging insects causing immunoglobulin (Ig) E-mediated reactions include honeybees, yellow jackets, yellow hornets, white- faced hornets, paper wasps, and fire ants. The identification of an IgE-mediated allergic disorder involves identifying the allergen, estabishing a causal relationship between the allergen and the reaction, and demonstrating the presence of specific IgE via immediate type skin testing or in vitro testing. Indications for immediate type skin testing include: 1. Identification of aeroallergen triggers in patients who have asthma 2. Allergic rhinitis that is not controlled with usual medications or if specific avoidance (eg, pet dander) is desired 3. Food allergy 4. Insect sting allergy 5. Vaccine, drug, or latex allergy 6. Evaluation for moderate-to-severe atopic dermatitis 7. Other conditions, including allergic fungal sinusitis, allergic bronchopulmonary aspergillosis, and eosinophilic esophagitis The decision to perform skin or in vitro testing depends on the age of the patient, the desire to start allergen immunotherapy, time since the reaction, and severity of the reaction. Allergy skin testing can be performed at any age, but infants and toddlers generally do not tolerate intradermal skin testing well and may not be able to communicate to their parent/clinician if they are developing a reaction during testing. In addition, clinicians may elect to start with in vitro testing in patients who have experienced life-threating reactions, as described in the vignette. Unfortunately, both skin testing and in vitro testing, when used alone for assessment of insect sting allergy, may provide false-negative results in up to 25% of patients. In cases of anaphylaxis, if the results of the initial test (skin or in vitro) are negative, the second testing modality should be undertaken. If testing is performed too soon (ie, within 2 weeks of the reaction), results may be negative due to depletion of mast cell mediators. Generally, skin testing should be performed 4 to 6 weeks after a sting reaction. Current guidelines recommend that patients who experience less severe reactions (eg, local or normal reactions, large local reactions, or cutaneous-only symptoms in children younger than than 16 years of age) do not require testing because of their low risk for future anaphylaxis. Epidemiologic studies have demonstrated that 25% to 50% of individuals can develop specific IgE to stinging insects, even after a normal or local reaction. However, such individuals (local reaction only) should not be tested, based on their normal reactions, and no specific avoidance measures or immunotherapy are recommended. Finally, when flying insect testing is performed, a complete set of the five Hymenoptera venoms (honey bee, yellow jacket, white-faced hornet, yellow hornet, wasp) should be used unless the specific insect is captured and identified by an entomologist. 11. Question 207 (2010) ANSWER: A - a high-dose inhaled steroid and long-acting beta agonist Based on the 2007 National Asthma Education and Prevention Program Expert Panel Report 3 Guidelines for the Diagnosis and Management of Asthma, the 12-year-old girl described in the vignette has severe persistent asthma. A stepwise approach is used to identify the severity of asthma in a new patient and determine the level of control. This stepwise approach accounts for patient's treatment responses and changes that often occur over time. The choice and schedule of medications is determined by the level of asthma severity and asthma control. Severe persistent asthma in children 12 years of age or older requires the initiation of step 4 or step 5 therapy (Item C207). The preferred treatment includes a medium- to high-dose inhaled corticosteroid plus a long-acting beta agonist (LABA). Omalizumab is an additional therapy that could be considered for this girl if she had allergic asthma, with evidence of specific sensitization to associated allergens and an appropriate total serum immunoglobulin E concentration. A medium-dose inhaled corticosteroid plus an oral leukotriene antagonist is an alternative to the previously noted regimen but is not the first choice. An oral leukotriene antagonist or oral theophylline as monotherapy are only appropriate for step 2 therapy. In asthma, exposure to allergens leads to an early airway response that develops fully within 10 to 20 minutes. In addition, a late airway response can occur and develop fully 3 to 8 hours after exposure. Oral and inhaled glucocorticoids inhibit the late-phase reaction but not the early-phase reaction. Inhaled short-acting and long-acting beta-adrenergic agents are potent inhibitors of the early-phase reaction. Leukotriene receptor antagonists (montelukast, zafirlukast) and leukotriene synthesis inhibitors (zileuton) also block the early-phase response and may have a mild impact on the late-phase response. 12. Question 223 (2010) ANSWER: B – intermittent The 2007 National Asthma Education and Prevention Program Expert Panel Report 3 for the Diagnosis and Management of Asthma (ERP3) continues to provide a framework for the determination of asthma severity and the initiation of appropriate therapy. EPR3 advises assessment of baseline asthma severity when initiating therapy, then monitoring asthma control while adjusting stepwise therapy to prevent functional impairment and minimize the risk of an exacerbation (Item C223). The new guidelines separate children into three groups: 0 through 4 years, 5 through 11 years, and 12 years and older. Based on an assessment of the impairment and risk, the severity of asthma experienced by the 12-year-old boy described in the vignette is categorized as intermittent. The nomenclature has changed from mild intermittent to intermittent as clinicians need to recognize that intermittent symptoms may be mild, moderate, or severe. Characteristics of intermittent asthma, as seen in the child in the vignette, include normal pulmonary function test results, daytime symptoms fewer than 2 days per week, and nighttime symptoms fewer than 2 days per month. Step 1 therapy for intermittent asthma involves using an as-needed short-acting bronchodilator. Once a child is diagnosed with asthma, the frequency of follow-up can be based on asthma severity and level of control. Exercise is a common trigger of asthma for children. Approximately 70% to 90% of children who have asthma are believed to have symptoms of exercise-induced asthma (EIA). Although the child in the vignette may have exercise-induced symptoms, a classification of EIA is less accurate than intermittent asthma because the child has symptoms outside of exercise (ie, at night). Because up to 40% of children who have allergic rhinitis have some degree of asthma and 60% to 80% of children who have asthma have allergic rhinitis, asking about other atopic diseases is recommended. 13. Question 254 (2010) ANSWER: B - epinephrine reaches higher peak plasma concentrations if injected into the thigh rather than the arm The prevalence of food allergies has continued to increase over the past 3 to 4 decades. Specifically, many children, parents, and school officials have been faced with the need to know about and understand how to recognize and appropriately treat food anaphylaxis in the school. Education and counseling of school officials and health-care clinicians is paramount to reduce morbidity and mortality from food anaphylaxis. The most common antigenic triggers of anaphylaxis are foods, drugs, insect venom, radiocontrast media, and latex. After exposure to an antigenic trigger, symptoms generally develop within 5 to 30 minutes, although symptoms can occur up to several hours after the exposure. Severe allergic reactions usually occur after binding of specific immunoglobulin (Ig) E to the high-affinity IgE receptor, with subsequent cross-linking of receptors and mediator release (eg, histamine, tryptase) from mast cells and basophils. Cutaneous manifestations such as urticaria, flushing, pruritus, and angioedema are the most common symptoms in anaphylaxis, occurring in 80% to 90% of episodes. Respiratory symptoms such as dyspnea, wheezing, shortness of breath, and cough are the next most frequent symptoms. Cardiovascular symptoms include cardiovascular collapse, tachycardia or relative bradycardia, and arrhythmias. Among the gastrointestinal manifestations are nausea, vomiting, diarrhea, abdominal pain, and cramping. Finally, many patients complain of either a metallic taste or "a sense of impending doom." Appropriate treatment of anaphylaxis consists of early administration of epinephrine. Because anaphylaxis can occur in the absence of a health-care professional such as at school, home, or a birthday party, children at risk always should have self-injectable epinephrine nearby. Although parents or other adults may be reluctant to inject a child with epinephrine, this agent, not an antihistamine, is the drug of choice for anaphylaxis. In the past, outpatient administration of epinephrine was subcutaneous, but research has demonstrated that intramuscular injection, specifically in the thigh, is the preferred route and location due to higher and faster peak plasma concentration. If epinephrine is administered, parents or school personnel should follow an emergency action plan. This should involve calling emergency services to evaluate the child and transport him or her to the emergency department for further evaluation. The effects of a single dose of epinephrine typically last for 5 to 15 minutes; up to 20% of individuals experiencing anaphylaxis may require a second epinephrine dose. When symptoms persist, a second (or third) dose should be administered, even if the parent or school professional still is awaiting the ambulance. Although epinephrine always is the drug of choice in anaphylaxis, glucagon may be required in refractory cases for patients using beta blockers. Self-injectable epinephrine should be available for all locations (ie, the patient usually carries one to two injectors), but leaving the device in the car is not recommended because extreme temperature changes can decrease the efficacy. Recommended storage temperatures are 20° to 25°C at home and 15°to 30°C during trips outside the home, school, or workplace. Approximately 5% to 20% of patients who suffer initial anaphylactic events can experience a "late- phase" response 4 to 24 hours later in which symptoms such as flushing, pruritus, or airway obstruction recur. Such later symptoms result from the recruitment of inflammatory cells after the initial hypersensitivity response. 14. Question 57 (2010) ANSWER: A – aspiration pneumonia The care of the technology-dependent child represents a considerable challenge for families and clinicians. The exact number of such children is unknown, but recent estimates suggest that they represent up to 20% of patient discharges from tertiary children's hospitals. Anatomic abnormalities, impaired neurologic status, loss of normal oromotor coordination, gastroesophageal reflux, and the presence of devices such as nasoenteric tubes and tracheostomies can lead to recurrent aspiration of gastric or upper airway secretions among such children. Aspiration can lead to a variety of respiratory problems, including wheezing, coughing, apnea, laryngospasm, and recurrent pneumonias. Tracheostomy tubes, even cuffed tubes, do not prevent aspiration and, in fact, may increase the risk in some patients due to desensitization of the larynx and loss of protective reflexes in combination with uncoordinated laryngeal closure. The child described in the vignette has a history of coughing with feedings and now has signs of an acute respiratory infection that include fever, tachypnea, and increased respiratory rate. Her chest radiograph demonstrates a diffuse right upper lobe infiltrate in a location consistent with aspiration pneumonia and no evidence of a pneumothorax (Item C57A) Congenital lobar emphysemas typically present with respiratory distress by 6 months of age. Radiographic findings include hyperinflation of the affected lobe with resultant atelectasis of adjacent lobes and shifting of the mediastinum away from the lesion (Item C57B). Chest radiography in viral infection typically shows hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing, and pulmonary hemorrhage is characterized by diffuse consolidation with a "ground glass" appearance. 15. Question 89 (2010) ANSWER: A – elevated level of carboxyhemoglobin Pulse oximetry has gained widespread acceptance, often is considered the "fifth vital sign," and has proven extremely useful in recognizing hypoxemia and decreasing critical airway events. Pulse oximetry uses red and infrared light to measure the level of oxygenated and deoxygenated hemoglobin. The amplitudes of the light signals are measured and mathematically calculated to express the percentage of oxygen saturation. Despite its enormous value, pulse oximetry has not been demonstrated to reduce mortality and has several key limitations. First, it does not measure ventilation and may falsely reassure clinicians about the adequacy of the patient's overall respiratory status. In addition, pulse oximetry can yield falsely low saturations in critically ill patients who have vasoconstriction, poor perfusion, hypothermia, or arrhythmias. Inaccurate readings also may result from ambient light interference or patient movement, inability to discriminate values below 70% accurately, interference by venous pulsations with tricuspid regurgitation, and the presence of abnormal hemoglobin such as carboxyhemoglobin and methemoglobin. Arterial blood gases with co-oximetry measurements should be obtained when the pulse oximetry reading does not correlate with clinical findings. The child described in the vignette does not demonstrate any evidence of shock or impaired cardiac performance. She has been rescued from a house fire and, therefore, is at high risk of carbon monoxide poisoning. Pulse oximetry cannot distinguish carboxyhemoglobin from oxyhemoglobin, resulting in a falsely high reading. Methemoglobinemia usually is caused by drug exposure or congenital enzymatic defects. Because methemoglobin is read as both oxyhemoglobin and deoxyhemoglobin by pulse oximeters, the saturation reading is generally around 85%. Fetal hemoglobin has little effect on the accuracy of pulse oximetry. In addition, the child in the vignette is 1 year of age and would be expected to have a trivial concentration of fetal hemoglobin. Finally, pulse oximetry does discriminate values greater than 90% accurately, but at higher values (≥95%), large fluctuations in PaO2 can occur with only small changes in oxygen saturation. 16. Question 98 (2010) ANSWER: B – apnea of prematurity Central apnea represents a total cessation of respirations and is mediated through mechanisms that affect the neural integration of sensory input (stretch receptors, chemoreceptors, and baroreceptors) and the central nervous system's efferent signaling for inspiration. By definition, such cessations of respiration last 20 seconds or longer or if they are less than 20 seconds in duration, are associated with cyanosis or bradycardia. The newborn described in the vignette displays central apnea with cyanosis and bradycardia. Apnea of prematurity, a form of central apnea, is considered a diagnosis of exclusion, and other potential contributing factors must be ruled out. It is treated effectively and safely with the methylxanthine caffeine. Central apnea is a common respiratory disorder among very low-birthweight preterm infants, typically appearing in the first 2 weeks of postnatal life. It must be evaluated within the context of the individual newborn's medical history and clinical setting. In addition, it must be distinguished from obstructive apnea, which is often due to neck flexion with positioning; gastroesophageal reflux with reflex glottic closure and cessation of airflow; and mechanical obstruction of the trachea or larynx. Numerous conditions may lead to central apnea: Sepsis, meningitis, or necrotizing enterocolitis Prolonged hypoxemia (lung disease, patent ductus arteriosus, profound anemia) Central nervous system depressant effects of certain medications (opioids, barbiturates, and benzodiazepines) Intracranial hemorrhage (including intraventricular, subdural, or subarachnoid hemorrhage) Hydrocephalus (including posthemorrhagic hydrocephalus) Electrolyte abnormalities Hypoglycemia Temperature instability (hypothermia or hyperthermia) Prematurity and immature respiratory drive Anemia of prematurity may contribute to apnea when it is profound (hemoglobin characteristically <7 g/dL [70 g/L]), but this is a late phenomenon (occurring after 2 to 4 weeks of postnatal age). Because the infant is receiving intravenous alimentation and some enteral feeding, it is unlikely that he is experiencing hypoglycemia. Necrotizing enterocolitis is very uncommon in the first 3 days after birth, and its association with apnea characteristically is in the context of a systemic illness, presenting with shock and lethargy. Sepsis may cause apnea, but the newborn described in the vignette does not exhibit any other clinical signs of sepsis. 17. Question 116 (2010) ANSWER: D – foreign body aspiration Cough and wheezing are common presentations in small children and infants. Although the most common causes involve asthma and bronchiolitis, tracheal and esophageal foreign bodies may present with the acute or subacute onset of cough and wheezing, especially in the older infant and toddler. The age, lack of symptoms since age 3 months, and abrupt onset of symptoms after eating a food that could be aspirated, as described for the boy in the vignette, suggest foreign body aspiration rather than the other more indolent causes. Contrary to popular belief, the aspiration of a small foreign body, including food (such as seeds or nuts) is as common in the left as the right mainstem bronchus in young children because the bifurcation of the trachea remains symmetric until the aortic knob grows larger in later childhood. Typically, a chest radiograph may not disclose air trapping for up to 1 day after the aspiration, despite the initial coughing. A careful history must be obtained for all children who have abrupt onset of cough and wheezing, and children whose histories strongly suggest foreign body aspiration should undergo prompt rigid bronchoscopy (Item C116). The child in respiratory distress should not be sent to the radiology department but should have expiratory and inspiratory anteroposterior chest radiography performed in the emergency department. Children who have aspirated foreign bodies are at high risk for developing secondary bacterial pneumonia. An esophageal foreign body, most often a coin, also may cause wheezing, but commonly patients also have vomiting or an inability to tolerate solid foods. When the foreign body remains in the upper half of the esophagus, the trachea may be compressed directly in some children, especially infants. Although bacterial pneumonia occasionally presents with wheezing (especially in the child who has asthma) and wheezing may be seen with community-acquired pneumonia caused by Mycoplasma and Chlamydia pneumoniae, other findings, such as fever, and bilateral signs upon auscultation of the chest, often are present. Cystic fibrosis should be considered in children who have persistent pulmonary disease, especially in conjunction with failure to thrive or diarrhea. 18. Question 132 (2010) ANSWER: D – may be efficacious in monitoring preterm infants who have hypoxia due to apnea of prematurity Although many parents believe that the use of an infant cardiorespiratory monitor in the home after an acute life-threatening event (ALTE) may be lifesaving, there is no evidence to support this belief. However, there is some evidence supporting the use of home apnea monitoring for an infant who has apnea of prematurity accompanied by hypoxia that responds to stimulation when the parents are trained to respond appropriately to emergencies. Monitoring is continued until 2 to 3 months have passed without an apneic episode. Skills of communication and professionalism are very important in assisting parents and other health-care professionals in understanding the use of evidence-based medicine to assign benefit and risk determinations to specific diagnostic and management strategies. In particular, the use of a home apnea monitor for an infant not proven to have a risk of recurrent paroxysmal cardiorespiratory event may increase the possibility of harms such as vulnerable child syndrome, parental anxiety and depression, and unnecessary administration of cardiopulmonary or other resuscitative efforts because false alarms and instrument malfunction are far more common than reversible infant cardiorespiratory events. There is no evidence that using a home apnea monitor reduces the risk of sudden infant death syndrome (SIDS) for a child who has apnea of prematurity, prior ALTE, or a sibling who suffered SIDS. Home monitoring will not prevent future episodes of ALTE in the child who has gastroesophageal reflux. Available evidence has failed to demonstrate a conclusive association between gastroesophageal reflux and ALTE. 19. Question 137 (2010) ANSWER: D – cystic fibrosis The child described in the vignette was admitted to the pediatric intensive care unit for bronchiolitis, but her history of failure to thrive and malabsorption as well as cystic lesions on radiologic imaging are consistent with cystic fibrosis. Cystic fibrosis can have a variety of presentations, including failure to thrive, delayed passage of stool, abnormal stools, rectal prolapse, and electrolyte abnormalities, but acute or chronic respiratory symptoms account for more than 50% of all presentations. Cough frequently is the first respiratory symptom, but progression to wheezing, shortness of breath, and recurrent pneumonia is common. Infants younger than 1 year of age can have bronchiolitis with wheezing, as described for the child in the vignette. Radiographic findings include hyperinflation, bronchial thickening, and patchy atelectasis. Progressive disease is evidenced by cyst formation, bronchiectasis, and lobar atelectasis. Severe complications of pulmonary disease that may be life-threatening can include development of pneumothoraces, cor pulmonale, and hemoptysis. Congenital disorders of the lung such as congenital cystic adenomatoid malformation, congenital lobar emphysema (Item C137), or pulmonary sequestration may present as respiratory distress during infancy, but they generally are not associated with malabsorption or failure to thrive. Clostridium difficile infection, which usually develops following antibiotic usage, can cause foul- smelling diarrhea, but failure to thrive is not a characteristic finding. 20. Question 140 (2010) ANSWER: B – endotracheally intubate the child The sudden deterioration and development of toxicity 5 days after the onset of an apparent crouplike illness described for the boy in the vignette is most consistent with development of bacterial tracheitis. The stridor, retractions, and decreased oxygen saturation all are consistent with this diagnosis. The rapidity of symptom progression and potential for increased purulent secretions to obstruct the airway mandate early endotracheal intubation to maintain and clear the airway. Parenteral antibiotic therapy, including coverage for Staphylococcus aureus, is another appropriate component of treatment. Of note, bacterial tracheitis is a potential complication of measles infection. A prolonged period of intubation may be necessary until the secretions clear with antimicrobial therapy. Although dexamethasone may be indicated for treatment of viral croup, the duration of illness and acute deterioration described for this boy argue for an alternative diagnosis. A lateral neck radiograph and pulmonary function testing are not helpful in the diagnosis of bacterial tracheitis and might be dangerous in a potentially critically ill patient by delaying antibiotic therapy and airway control. An emergency tracheostomy is not indicated if endotracheal intubation can be accomplished successfully. However, a tracheostomy may be necessary and possibly lifesaving in the presence of a fixed obstruction in the upper airway, such as epiglottitis, to bypass the lesion. Epiglottitis typically presents acutely, with rapid progression over hours from onset of symptoms to toxicity and impending airway obstruction. Fortunately, the advent of the conjugate Haemophilus influenzae type b vaccine has made acute epiglottis an extremely rare entity. 21. Question 201 (2010) ANSWER: C - emergent otolaryngology and anesthesia consultation Epiglottitis is a medical emergency. The incidence of this disease has significantly decreased since the introduction of the Haemophilus influenzae type b vaccine, and the most common infectious pathogens now are Streptococcus pneumoniae, group A beta-hemolytic Streptococcus, and Staphylococcus aureus. Often, the infection involves the entire supraglottic area, not just the epiglottis, and is called supraglottitis. The current incidence in children younger than 5 years of age is approximately 1.3 cases per 100,000, a decrease from the 40 cases per 100,000 seen 20 years ago. Affected patients, typically between 2 and 8 years of age, usually present with the rapid onset of fever, sore throat, and the "four Ds" (drooling, dysphagia, dysphonia, and dyspnea), as described for the boy in the vignette. Patients may assume a position of comfort by sitting upright, leaning forward, and bracing themselves with their arms, known as the "tripod position." Clinicians must be vigilant for atypical presentations, especially among children younger than 2 years of age. Airway management for this disease is paramount. Direct examination of the airway under anesthesia (with the availability of personnel who can perform a tracheostomy if needed) is the preferred management for suspected cases that involve signs of respiratory compromise (Item C201A). Therefore, an emergent otolaryngology and anesthesia consultation is the most appropriate next step for the boy in the vignette. An endotracheal tube that is 0.5 to 1 mm smaller than usual for age generally is needed. Cultures of the supraglottic area can be obtained at the time of intubation and broad-spectrum antibiotics effective against beta-lactamase-producing organisms can be initiated. Lateral radiographs are diagnostic (Item C201B), as in this case, but should be deferred in children strongly suspected of having epiglottitis until the proper personnel and equipment are available to secure the airway if needed. Invasive procedures, including phlebotomy, obtaining vascular access or a throat culture, or intramuscular administration of medications, should be deferred until the airway is secured properly. In addition, neither penicillin nor dexamethasone is indicated for the initial treatment of epiglottitis. 22. Question 227 (2010) ANSWER: E – sweat test Cystic fibrosis is an autosomal recessive disorder characterized primarily by chronic pulmonary disease and pancreatic insufficiency. A defect in chromosome 7 causes abnormal regulation of the cystic fibrosis transmembrane conductance regulator (CFTR), which transports chloride in luminal areas such as airways, intestines, sweat ducts, and pancreatic ducts. Fluid secretions become thickened, leading to multisystem mucus plugging. Varying degrees of clinical features may be seen because of the many mutations that can occur in the CFTR gene. The clinical features that can be present include recurrent upper and lower respiratory tract infections (especially due to Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae), steatorrhea (from fat malabsorption) and meconium ileus, cholelithiasis, and male infertility. Deficiencies of vitamins A, D, E, and K are present because of fat malabsorption. Failure to thrive is a common presenting feature because of chronic malabsorption and frequent infections. Laboratory testing may reveal hypoproteinemia, anemia, and hypochloremic metabolic alkalosis. Because the boy described in the vignette has features that are most consistent with cystic fibrosis, a sweat chloride determination (sweat test) is the most appropriate test to make the diagnosis. A sweat test involves the application of pilocarpine to the skin to stimulate sweat production, followed by measurement of the chloride concentration in the sweat. A positive result is greater than 60 mEq/L. False-positive results may be seen in Addison disease, hypothyroidism, and some glycogen storage diseases. False-negative results may be seen if the infant is malnourished or if inadequate sweat volume is obtained, as in the neonatal period or with technical errors. Treatment of cystic fibrosis includes the administration of pancreatic enzymes, increased caloric intake (especially from fat), intensive antibiotic therapy for respiratory infections, and aggressive airway clearance regimens. Inhaled antibiotics, such as tobramycin, used every other month have been shown to reduce the incidence of pulmonary infections. Giardia infections are caused by a protozoan that can be transmitted by the ingestion of cysts from contaminated water. Clinical features include watery diarrhea, abdominal pain, and bloating. Steatorrhea and respiratory symptoms are not seen. The diagnosis may be made either by viewing the cysts in the stool or by immunosorbent assay. Antigliadin antibodies are helpful in making the diagnosis of celiac disease, which causes chronic diarrhea and failure to thrive after the introduction of gluten to the diet. Alpha-1-antitrypsin concentrations may be elevated in the stool if a protein- losing enteropathy is present. This may be seen in cystic fibrosis, as well as other diseases such as allergic gastroenteropathy and inflammatory bowel disease, but the finding is not diagnostic of cystic fibrosis. Stool should be evaluated for ova, cysts, and parasites if infections such as cryptosporidiosis are suspected. 23. Question 229 (2010) ANSWER: A – barium swallow A number of clinical entities are responsible for stridor in children, but when stridor accompanies feeding, as described for the infant in the vignette, vascular ring is an important potential cause. Vascular rings occur when the vascular structures of the aorta and pulmonary artery completely encircle the trachea and the esophagus (Item C229A). Virtually every vascular ring can lead to a similar set of clinical findings. For most affected patients, the intracardiac anatomy, physiology, and hemodynamics are normal. When symptoms do occur, they typically result from compression of the trachea or the esophagus. The most common symptoms related to tracheal compression are stridor, wheezing, and dyspnea, all of which may be exacerbated by feeding. The age of onset and type of symptoms depend on the anatomic type and severity of the vascular ring. If the anomaly is unrecognized, patients may have recurrent pneumonia and progressive difficulty with feeding. Radiography of the chest may be helpful and often can identify the sidedness of the aortic arch, which is defined by the mainstem bronchus that it crosses. However, barium swallow is the most useful study (Item C229B). When a vascular ring is suspected, both the posterior-anterior and lateral views should be obtained, and fluoroscopy should be considered. Computed tomography scan can be a useful diagnostic study for the patient who has stridor and a vascular ring, but it exposes the young patient to a much higher amount of ionizing radiation than does barium swallow (Item C229C). Because most patients who have vascular rings have normal intracardiac anatomy, electrocardiography is not helpful in determining the cause of the stridor. Radiography of the neck and the sweat test are not diagnostic for a vascular ring. 24. Question 233 (2010) ANSWER: B - bronchoscopy may be useful for both diagnosis and treatment Bacterial pneumonia is a significant cause of morbidity and mortality worldwide, especially in developing countries. Most cases of pneumonia in the United States are treated on an outpatient basis. The incidence of complicated pneumonias has increased, due in part to the increasing prevalence of both antibiotic-resistant and more invasive pathogens. Complications of pneumonia include pleural effusions, empyema, lung abscess, necrotizing pneumonia, pericarditis, pneumothoraces, bronchopleural fistulas, and hematogenous spread to other sites. Bronchopleural fistulas, the development of a connection between the bronchial tree and pleural space, are rare but are associated with a high rate of morbidity and mortality (rates of 30% to 70% have been reported). Most commonly, they follow a pulmonary resection, but they can occur with necrotizing bacterial pneumonia or as a result of persistent pneumothoraces. Bronchopulmonary fistulas generally are recognized in the intensive care unit patient by the presence of a persistent air leak, as described for the boy in the vignette. Such fistulas rarely heal without intervention, and they often prove difficult to manage. Frequently the diagnosis is clinical, but they are localized definitively with bronchoscopy. Chest computed tomography scan has shown promise in both diagnosing and planning surgical correction of complicated cases. Management strategies include insertion or continuation of chest tubes, decreasing mechanical ventilator support to the lowest pressures needed to allow spontaneous healing, differential lung ventilation, application of sealants through a bronchoscope, and surgical closure. Surgical success rates of 80% to 95% rate have been reported in adults, depending on the cause. 25. Question 249 (2010) ANSWER: C – computed tomography scan of the chest Congenital malformations of the lung usually present during the first 6 postnatal months, but symptoms can be identical to more common pediatric conditions, such as asthma, viral infections, or bacterial pneumonias. Congenital lung malformations include pulmonary hypoplasia (reduction in bronchiole number and alveoli), pulmonary agenesis (absence of vasculature and lung tissue), pulmonary aplasia (presence of rudimentary bronchus but absence of vasculature and lung tissue), congenital cystic adenomatoid malformation (dysplastic lung tissue), congenital lobar emphysema (idiopathic hyperinflation of one or more lobes), and pulmonary sequestration (lung tissue that has a systemic arterial supply instead of pulmonary arterial supply and generally lacks bronchial communication). The boy described in the vignette has a classic presentation of pulmonary sequestration, which accounts for 6% of all congenital lung malformations, occurs more commonly in the left lower lobe, and has a male predominance. Sequestrations are classified as either intrapulmonary or extrapulmonary, according to their presence inside or outside the visceral (inner) pleura. Affected infants and children often present with chronic cough and recurrent respiratory infections in the same anatomic location. Physical examination findings include dullness to percussion, with decreased aeration over the affected area. Crackles frequently are audible during infection. Patients who have large systemic arterial-to-venous shunts may present with a systolic murmur and exercise intolerance. Radiographs demonstrate consolidation of the affected area, but often show air-filled cystic lesions during active infections (Item C249). Computed tomography scan is used to establish the diagnosis and plan surgical treatment, if indicated. Aortography may be useful to determine vascular supply, but computed tomography with angiography is preferable and is the initial step in the evaluation. Administration of amoxicillin with future follow-up is neither curative nor appropriate. Thoracentesis is not helpful in establishing the diagnosis. The child does not have symptoms consistent with gastroesophageal reflux and, therefore, a pH probe is not indicated.