Secrets – Pediatric: Pulmonology

Secrets – Pediatric: Pulmonology

ALLERGIC RHINITIS
1. How common is allergic rhinitis?
Very common. Up to 40% of children experience rhinitis, which is the most common manifestation of allergic disease and one of the most common chronic diseases of childhood.
2. In addition to chronic or recurrent nasal congestion, what features on history and physical examination suggest allergic rhinitis?
• “Allergic facies”: Open mouth, midface hypoplasia
• “Allergic nasal crease”: Nasal crease on bridge of nose as a result of chronic upward rubbing with the palm of the hand (the allergic salute)
• Diminished sense of taste and smell
• Dental malocclusion
• Allergic “shiners” (dark circles under the eyes)
• Multiple infraorbital folds
• Cobblestoning of the posterior oropharynx (Fig. 16-1)
• Pale, boggy appearance of the nasal mucosa

Figure 16-1. Cobblestone appearance of the posterior pharynx from postnasal drip. (From Terasaski G, Paauw DS: Evaluation and treatment of chronic cough, Med Clin North Am 98:391–403, 2014.)

3. What are three early-life risk factors for allergic rhinitis?
1. Male gender (Females have a higher incidence of rhinitis in adulthood.)
2. Not having early contact with siblings at home or children in daycare
3. Not having early contact with pets or not living on a farm

Matheson MC, Dharmage SC, Abramson MJ, et al: Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study—an international population-based cohort study, J Allergy Clin Immunol 128:816– 823, 2011.

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4. How does the time of year help identify the potential cause of allergic rhinitis?
Tree pollen is usually associated with the onset of the growing season. After local tree pollination, grass pollens appear; this may occur earlier in locales where there are short winters. Weed pollen other than ragweed, is associated with the late-summer pollen peak. In the autumn, ragweed is the major pollen allergen. It pollinates from mid-August until the first freeze in most of the U.S. Counts are especially high in eastern and central North America. Fungal aeroallergens span the growing season. Relative concentrations of household animal allergens, dust mites, and indoor fungi generally increase when doors and windows are closed. However, dust mites and molds proliferate in areas of high humidity and may cause perennial symptoms.

Naclerio R, Solomon W: Rhinitis and inhalant allergens, JAMA 278: 1842–1848, 1997.

5. When are allergy blood tests used?
• A patient is taking a medication that blocks allergy skin testing, such as an antihistamine that cannot be stopped for at least 3 days.
• A patient has a skin condition such as eczema or psoriasis without sufficient unaffected areas to do skin testing
• Blood testing would be better tolerated, such as in an infant or young child.

American College of Allergy, Asthma and Immunology: www.acaai.org. Accessed on Jan. 13, 2015.

6. What is an antigen-specific IgE ImmunoCAP?
An IgE ImmunoCAP (Thermo-Fisher Scientific Inc., Uppsala, Sweden) is an in VITRO automated laboratory method used to quantify the amount of allergen-specific IgE in a patient’s serum.
The test allergen is bound to a solid phase matrix and then incubated with the serum. If it contains the allergen-specific IgE, the patient’s IgE will bind to the ImmunoCAP antigen. Nonspecific IgE is removed by washing. Fluorescent-labeled anti-IgE is then added and binds to the IgE-antigen complex. Fluorescence is measured and compared to a standard curve.

Johansson SG: ImmunoCAP specific IgE test: an objective tool for research and routine allergy diagnosis,
Expert REV Mol Diagn 4:273–279, 2004.

7. Summarize the pros and cons of skin testing versus in vitro testing (e.g., IgE ImmunoCAP) for allergies
In VITRO tests
• No risk for anaphylaxis
• Results not influenced by medications (e.g., antihistamines), dermatographism, or extensive dermatologic disease
• More costly
• Better predictive value for some common food allergens
Skin testing
• Less costly
• More sensitive than in VITRO tests
• Results immediately available

8. What are the recommended treatments for children with allergic rhinitis?
• Environmental control measures for allergen avoidance are the mainstay of treatment. Relevant allergens are recommended for exposure reduction on positive skin or serum-specific IgE testing correlated with the presence of symptoms on allergen exposure.
• Pharmacotherapy, including nasal corticosteroid sprays, antihistamines (given orally or by
nasal spray), oral antileukotrienes, or combinations of these medications are effective treatments.
• Immunotherapy is reserved for those with persistent symptoms despite the above treatment and for those who want control of symptoms with less medications.

American Academy of Allergy, Asthma and Immunology: www.aaaai.org. Accessed on Jan. 13, 2015.

9. What are the major indoor (year-round) allergens?
House dust mites, animal danders, cockroach, and molds.

10. How can you decrease cat allergen in the home?
• Consider a “felinectomy.”
• Remove upholstered furniture, carpet, and other sources harboring the allergen.
• Use high-efficiency particulate air (HEPA) air filters and vacuum cleaners.
• Wash the cat weekly if feasible.

11. Is there truly a dog breed that is “hypoallergenic”?
Alas, the hypoallergenic dog appears to be a myth. Although certain dogs (e.g., poodles; Spanish waterdogs; Airedale terriers; and the newer hybrid, the Labradoodle) are commonly marketed as “hypoallergenic,” comparison of the quantity of the dog allergen (Can f 1) in hair and coat samples and in the surrounding surface environment found no differences compared with control breeds.
In the United States, about 78 million dogs occupy homes, so this is not good news to the 20% of the general population who may be allergic to dogs.

Vredegoor DW, Willemse T, Chapman MD, et al: Can f 1 levels in hair and homes of different dog breeds: lack of evidence to describe any dog breed as hypoallergenic, J Allergy Clin Immunol 130:904.e7–909.e7, 2012.

12. Which children should be considered for immunotherapy?
Allergen immunotherapy is an effective treatment for allergic rhinitis, asthma, and the prevention of venom anaphylaxis. It also may be of benefit in atopic dermatitis. For allergic rhinitis and allergic asthma, immunotherapy should be considered in patients who are not well-controlled despite attempts at allergen exposure reduction and pharmacotherapy or in patients who wish to take less medication. Subcutaneous or sublingual routes (for certain inhalant allergens) are approved in the United States. In children, immunotherapy has been shown to prevent the progression of allergic rhinitis to asthma and may prevent sensitization to new allergens in monosensitized individuals.

Jones SM, Burks W, Dupont C: State of the art on food allergen immunotherapy: oral, sublingual, and epicutaneous, J Allerg Clin Immunol 133:318–323, 2014.
Burks AW, Calderon MA, Casale T, et al: Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report, J Allergy Clin Immunol 131:1288–1296, 2013.

13. How common is exercise-induced bronchospasm in children with allergic rhinitis? Exercise is a trigger of bronchospasm in 40% to 50% of children with allergic rhinitis, compared with 90% of those diagnosed with asthma and 10% of those not known to have asthma or

respiratory allergies. Exercised-induced bronchospasm is defined as a 10% drop in FEV1 or peak expiratory flow rate from the value before exercise.

Randolph C: Exercise-induced bronchospasm in children, Clinic REV Allerg Immunol 34:205–216, 2008.

ASTHMA
14. If both parents are asthmatic, what is the risk that their child will have asthma?
The risk is 60%. For a child with only one parent with asthma, the risk is estimated to be about 20%. If neither parent has asthma, the risk is 6% to 7%.
15. When does asthma usually have its onset of symptoms?
About 50% of childhood asthma develops before the age of 3 years, and nearly all has developed by the age of 7 years. The signs and symptoms of asthma, including chronic cough, may be evident much earlier than the actual diagnosis but may be erroneously attributed to recurrent pneumonia.

American Lung Association: www.lungusa.org. Accessed on Jan. 13, 2015.

16. Which children with wheezing at an early age are likely to develop chronic asthma? Although about one-third of children will have an episode of wheezing before they are 1 year old, most (80%) do not develop persistent wheezing after age 3 years. Risks factors for persistence include the following:
• Positive family history of asthma (especially maternal)
• Increased IgE levels
• Atopic dermatitis
• Rhinitis not associated with colds
• Secondhand smoke exposure

Taussig LM, Wright AL, Holberg CJ, et al: Tuscon Children’s Respiratory Study: 1980 to present, J Allergy Clin Immunol
111:661–675, 2003.

17. What historical points are suggestive of an allergic basis for asthma?
• Seasonal nature with concurrent rhinitis (suggesting pollen)
• Symptoms worsen when visiting a family with pets (suggesting animal dander)
• Wheezing occurs when carpets are vacuumed or bed is made (suggesting mites)
• Symptoms develop in damp basements or barns (suggesting molds)
18. What are other potential triggers for asthma?
• Cold air
• Emotional extremes (stress, fear, crying, laughing)
• Environmental (pollutants, cigarette smoke)
• Exercise
• Foods, food additives
• Gastroesophageal reflux disease
• Hormonal (menstrual, premenstrual)
• Irritants (strong odors, paint fumes, chlorine)
• Medications (nonsteroidal anti-inflammatory drugs, aspirin, β-blockers)
• Substance abuse
• Upper airway infections (rhinitis, sinusitis)
• Weather changes

American Academy of Allergy, Asthma and Immunology: www.aaaai.org. Accessed on Jan. 13, 2015.

19. What distinguishes EIA from EIB?
Exercise-induced asthma (EIA) is a common component of those who have been diagnosed with asthma. Significant symptoms (e.g., cough, chest tightness, wheezing, dyspnea) are noted after

exercise in up to 90% of asthmatic children, although abnormal pulmonary function tests can be found in nearly 100% of these patients. Exercise-induced bronchospasm (EIB) now more commonly refers to those with airway narrowing in response to exercise who have not been diagnosed with asthma. Up to 12% of adolescent athletes and 40% of college varsity athletes may manifest EIB. Among atopic children, the incidence of EIB has been estimated to be as high as 40%.

Parsons JP, Kaeding C, Phillips G, et al: Prevalence of exercise-induced bronchospasm in a cohort of varsity college athletes, Med Sci Sports Exerc 39:1487, 2007.

20. What is the time course of EIB?
Symptoms, most commonly cough, peak 5 to 10 minutes after the conclusion of exercise and usually resolve within 30 to 60 minutes.
21. How is EIB diagnosed?
• Exercise challenge: EIB is likely if the peak flow rate or FEV1 drops by 15% after 6 minutes of vigorous exercise, either in a laboratory or field setting. This exercise can include jogging on a motor-driven treadmill (15% grade at 3 to 4 mph), riding a stationary bicycle, or running
up and down a hallway or around a track in field testing. The greatest reduction in EIB is usually seen 5 to 10 minutes after exercise. As further verification of the diagnosis, if the patient has developed a decreased peak flow (and possibly wheezing), two puffs of a β2-agonist should be administered to attempt to reverse the bronchospasm.
• Eucapnic voluntary hyperventilation (EVH) involves breathing a dry gas at an increased respiratory rate in an effort to induce bronchospasm and a decrease of FEV1 of >10%.
• Osmotic challenge is the inhalation of hypertonic saline or dry powder mannitol to induce
bronchospasm.
• Pharmacologic challenge is a direct measurement using agents that act on smooth muscle (e.g., histamine, methacholine). The threshold concentration required to induce bronchospasm is determined and compared with that required in healthy controls.

Cuff S, Loud K: Exercise-induced bronchospasm, Contemp Pediatr 25:88–95, 2008.

22. A 15-year-old with repeated shortness of breath after track practice has suspected exercise-induced bronchospasm, but pulmonary function tests are normal, bronchoprovocation testing is negative, and he has no response to treatment with asthma medications. What is a likely alternative?
Exercise-induced laryngeal obstruction (EILO). This group of diagnoses includes VOCAL cord dysfunction and exercise-induced laryngomalacia. In the former, during exercise, the vocal cords adduct during inspiration to cause shortness of breath, chest tightness, cough, or stridor. In the latter, there is inspiratory prolapse of supraglottic structures, which causes dyspnea and/or stridor. In both cases, there is paradoxic laryngeal motion—narrowing occurs when a bigger breath is taken. The precise reasons are unclear but may be related to smaller airway dimensions, inhibition of laryngeal reflexes, or impaired innervation and/or power of the laryngeal muscles. The gold standard test for diagnosis
is flexible nasoendoscopy with continuous video recording of the larynx throughout exercise.

Tilles SA, Ayars AG, Picciano JF, et al: Exercise-induced vocal cord dysfunction and exercise-induced laryngomalacia in children and adolescents: the same clinical syndrome? Ann Allergy Asthma Immunol 111:342–346, 2013.
Nielsen EW, Hull JH, Backer V: High prevalence of exercise-induced laryngeal obstruction in athletes, Med Sci Sports Exerc 45:2030–2035, 2013.

23. What mechanisms lead to airway obstruction during an acute asthma attack? The main causes of airflow obstruction in acute asthma are airway inflammation, including edema, bronchospasm, and increased mucous production. Chronic inflammation eventually results in airway remodeling, which may not be clinically apparent.
24. All that wheezes is not asthma. What are other noninfectious causes?
• Aspiration pneumonitis: Especially in a neurologically impaired infant or an infant with gastroesophageal reflux, and especially if there is coughing, choking, or gagging with feedings. If there is a clear association with feedings, consider the possibility of tracheoesophageal fistula.

• Bronchiolitis obliterans: Chronic wheezing often after adenoviral infection
• Bronchopulmonary dysplasia: Especially if there has been prolonged oxygen therapy or a ventilatory requirement during the neonatal period
• Ciliary dyskinesia: Especially if recurrent otitis media, sinusitis, or situs inversus is present
• Congenital malformations: Including tracheobronchial anomalies, tracheomalacia, lung cysts, and mediastinal lesions
• Cystic fibrosis: If wheezing is recurrent, and associated with failure to thrive, chronic diarrhea, or recurrent respiratory infections
• Congenital cardiac anomalies: Especially lesions with large left-to-right shunts
• Foreign-body aspiration: If associated with an acute choking episode in an infant >6 months
• Vascular rings, slings, or airway compression
25. How is the severity of an acute asthma attack estimated?
See Table 16-1.

Table 16-1. Classifying Severity of Asthma Exacerbations in the Urgent or Emergency Care Setting
SYMPTOMS AND SIGNS INITIAL PEF (OR FEV1)
CLINICAL COURSE
Mild Dyspnea only with PEF≤70% • Usually cared for at home
activity (assess predicted or • Prompt relief with inhaled SABA
tachypnea in personal • Possible short course of oral systemic
young children) best corticosteroids
Moderate Dyspnea interferes with or limits usual activity PEF 40-69%
predicted or personal best • Usually requires office or ED visit
• Relief from frequent inhaled SABA
• Oral systemic corticosteroids; some symptoms last for 1-2 days after treatment is begun
Severe Dyspnea at rest; interferes with conversation PEF <40%
predicted or
personal best • Usually requires ED visit and likely hospitalization
• Partial relief from frequent inhaled SABA
• Oral systemic corticosteroids; some symptoms last for >3 days after treatment is begun
• Adjunctive therapies are helpful
Subset: Life threatening Too dyspneic to speak; perspiring PEF <25%
predicted or
personal best • Requires ED/hospitalization; possible ICU
• Minimal or no relief from frequent inhaled SABA
• Intravenous corticosteroids
• Adjunctive therapies are helpful
ED emergency department; FEV1 forced expiratory volume in 1 second; ICU intensive care unit; PEF peak expiratory flow; SABA short-acting beta2-agonist.
Adapted from the National Asthma Education and PREVENTION Program Expert Panel Report 3, 2007.

26. Is a chest radiograph necessary for all children who wheeze for the first time?
A chest radiograph should be considered for a first-time wheezing patient in the following situations:
• Findings on physical examination that may suggest other diagnoses
• Marked asymmetry of breath sounds (suggesting a foreign-body aspiration)
• Suspected pneumonia
• History suggestive of foreign-body aspiration
• Hypoxemia or marked respiratory distress
• Older child with no family history of asthma or atopy
• Suspected congestive heart failure
• History of trauma that may have caused injury to the airway (e.g., burns, scalds, blunt or penetrating injury)

27. What are the usual findings on arterial blood gas sampling during acute asthma attacks?
The most common finding is hypocapnia (i.e., low PaCO2) because of hyperventilation and hypoxemia may also be present unless the child is being treated with oxygen. Hypercapnia is a serious sign that suggests that the child is tiring or becoming severely obstructed. This finding should prompt reevaluation and consideration of admission to a high-acuity unit.

28. What are the indications for hospital admission in children with asthma? After therapy in the emergency department, admission is advisable if a child has any of the following:
• Depressed level of consciousness
• Incomplete response with moderate retractions, wheezing, peak flow of <60% predicted, pulsus paradoxus of >15 mm Hg, SaO2 of 90% or less, PCO2 of 42 mm Hg or more
• Breath sounds diminished significantly
• Evidence of dehydration
• Pneumothorax
• Residual symptoms and history of severe attacks involving prolonged hospitalization (especially if intubation was required)
• Parental unreliability
An equally difficult (and very unpredictable) challenge relates in predicting which patients will relapse after responding to therapy and subsequently require hospitalization. This is a major problem because rates of relapse in asthma can approach 20% to 30%.

29. List the possible acute side effects of albuterol and other β-agonists
• General: Hypoxemia, tachyphylaxis
• Renal: Hypokalemia
• Cardiovascular: Tachycardia, palpitations, premature ventricular contractions, atrial fibrillation
• Neurologic: Headache, irritability, insomnia, tremor, weakness
• Gastrointestinal: Nausea, heartburn, vomiting Fortunately, these side effects are uncommon.

30. What is the role of magnesium sulfate in acute asthma attacks?
Magnesium sulfate is a known smooth muscle relaxant most commonly used in the treatment of preeclampsia. In asthmatic patients, when used in conjunction with standard bronchodilators and corticosteroids, intravenous magnesium sulfate can provide additional bronchodilation with a reduced likelihood of hospital admission. It is most commonly used when severely ill patients have failed to respond to conventional therapy. Inhaled magnesium sulfate as an adjuvant therapy in children is currently under study. Adult studies have demonstrated significant improvements in respiratory function and lower hospital admission rates.

Shan Z, Rong Y, Yang W, et al: Intravenous and nebulized magnesium sulfate for treating acute asthma in adults and children: a systematic review and meta-analysis, Resp Med 107:321–330, 2013.

31. How is chronic asthma severity classified among children 5 to 11 years of age? The National Heart, Lung, and Blood Institute and National Asthma Prevention Program (NAEPP) define severity in terms of impairment and risk. Four categories are listed: intermittent, mild persistent, moderate persistent, and severe persistent. Categorization which is also separately done for 0 to 4 years and ≤12 years, helps guide therapy (Table 16-2).

National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007, Bethesda, MD, August 2007, National Heart, Lung, and Blood Institute. NHLBI publication 08-4051. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed on Jan. 13, 2015.

32. What is the treatment of choice for patients with persistent asthma?
Inhaled corticosteroids. Daily administration significantly improves symptoms, reduces exacerbations, and allows healing of the chronic inflammatory changes that have taken place in

Table 16-2. Classifying Asthma Severity and Initiating Therapy in Children
CLASSIFYING ASTHMA SEVERITY AND INITIATING THERAPY IN CHILDREN
Persistent
Intermittent Mild Moderate Severe
Ages
COMPONENTS OF SEVERITY Ages 0–4 Ages 5–11 Ages 0–4 Ages 5–11 Ages 0–4 Ages 5–11 Ages 0–4 5–11
Impairment Symptoms 0≤2 days/week
≤ 2 days/week None

N/A ≤2 ×/month

Normal FEV1 between exacerbations
>80%

>85% >2 days/week but not daily 1-2 ×/month
>2 days/week but not daily Minor limitation

N/A 3-4×/month

>80%
>80% Daily
3-4×/month

Daily

Some limitation N/A Throughout the day
> 1 ×/week Often 7x/week

Several times per day

Extremely limited
N/A <60%
<75%
Nighttime awakenings > 1 ×/week
but not
nightly
Short-acting beta2-
agonist use for
symptom control
Interference with
normal activity
Lung function 60 — 80%
75 — 80%
• FEV1 (predicted)
or peak flow
(personal best)
• FEV1/FVC
Risk Exacerbations 0-1/year ≤2 exacerbations in
requiring oral 6 months requiring oral ≤2 ×/year
systemic synthetic corticosteroids (see notes)
corticosteroids or ≤4 wheezing Relative annual
(consider severity episodes/1 year lasting risk may
and interval since >1 day and risk factors be related
last exacerbation) for persistent asthma. to Fev1
FEV1 Forced expiratory volume in 1 second; FVC forced expiratory capacity; ICS inhaled corticosteroids; ICU intensive care unit; N/A not applicable.
Adapted from the National Asthma Education and PREVENTION Program Expert Panel Report 3, 2007.

the airways over time. Dosing and the use of adjunctive medications (e.g., long-acting inhaled
β2-agonists, leukotriene-receptor antagonists) depend on the severity of the persistence.

Bel EH: Mild asthma, N Engl J Med 369:549–557, 2013. Rachelefsky G: Inhaled corticosteroids and asthma control in children: assessing impairment and risk, Pediatrics 123:353– 366, 2009.

33. Do inhaled steroids affect growth in children?
Results are conflicting but tend to indicate that mild growth suppression occurs among children receiving moderate to high doses, particularly in children with more severe asthma and primarily during the first year of therapy (about 1 cm). The reduction in growth is generally not progressive. Asthma per se can also inhibit growth, and inhaled steroid therapy does not appear to affect eventual adult height. It is important that children who require the extended use of inhaled steroids are monitored for height and height velocity and also for cataracts.

Zhang L, Prietsch SO, Ducharme FM: Inhaled corticosteroids in children with persistent asthma: effects on growth,
Cochrane Database Sys REV 7:CD009471, 2014.
Kelly HW, Sternberg AL, Lescher R, et al: Effect of inhaled glucocorticoids in childhood on adult height, N Engl J Med 367:904–912, 2012.

34. What is anti-IgE treatment for asthma?
Omalizumab is a humanized monoclonal anti-IgE antibody approved for adjunctive therapy of severe persistent asthma in patients aged 12 years and older with an elevated total IgE and sensitivity to perennial allergens. It prevents free serum IgE from binding to its high-affinity receptors on mast cells and basophils. Omalizumab has been shown to reduce asthma exacerbations. It should be
considered as an add-on for children >6 years of age who have inadequately controlled severe persistent allergic IgE-mediated asthma who require continuous or frequent oral corticosteroids. Rarely,
symptoms of anaphylaxis may develop up to 24 hours after administration, so the clinician administering the drug should be prepared to treat anaphylaxis, and the patient should carry self-injectable epinephrine for 1 day after administration.

Normansell R, Walker S, Milan SJ, et al: Omalizumab for asthma in adults and children, Cochrane Database Syst REV 1: CD003559, 2014.

35. Is there a role for complementary and alternative medicines in the treatment of asthma?
There are no clear directions or guidelines for the use of complementary and alternative medicines
for children with asthma, although these therapies are often independently used by families. Hypnosis, yoga, relaxation techniques, acupuncture, and massage have shown benefit in some studies, but a review of studies involving mind-body techniques, relaxation, manual therapies, and diet has found a tendency to little or no significant difference between sham (placebo) and active therapy.

Snyder J, Brown P: Complementary and alternative medicine in children: an analysis of the recent literature, Curr Opin Pediatr 24:539–546, 2012.
Markham AW, Wilkinson JM: Complementary and alternative medicines (CAM) in the management of asthma: an examination of the evidence, J Asthma 41:131–139, 2004.

36. How useful are pulmonary function tests when evaluating and following children with asthma? Spirometry is used for both the diagnosis and monitoring of asthma in children 5 years of age and older. The diagnosis of asthma requires airflow obstruction with at least a 12% improvement, or reversibility, in FEV1 from baseline with the inhalation of a short-acting β-agonist. Patient history and physical examination do not adequately predict the degree of a patient’s airflow obstruction. Spirometry is
also used to monitor asthma after diagnosis and treatment. The goals of asthma therapy include normal or near-normal lung function with treatment. Spirometry should be performed on the patient after treatment has been initiated or changed, based on abnormal lung function, to assess improvement. It should also be performed during periods of prolonged loss of asthma control. Otherwise, in

symptomatically controlled patients, it should be repeated at least yearly to monitor the patient long term. Hand-held peak flow measurements are useful for monitoring patients, but not for initial diagnosis.

National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007, Bethesda, MD, August 2007, National Heart, Lung, and Blood Institute. NHLBI publication 08-4051. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed on Jan. 13, 2015.

37. What proportion of asthmatic children “outgrow” their symptoms?
Popular pediatric teaching has been that most children with asthma outgrow their symptoms. However, studies suggest that this is erroneous and that only 30% to 50% become free of symptoms, primarily those with milder disease. Many children who appear to outgrow symptoms have recurrences during adulthood. Studies also indicate that many infants who wheeze with viral infections and are asymptomatic between illnesses tend to outgrow their asthma. Children with (1) early-onset asthma
(age< 3 years) with a positive parental history for asthma, (2) atopic dermatitis, or (3) sensitization to aeroallergens are more likely to have persistent or recurrent bronchospasm. Although the overall
trend is for asthma to become milder, a large percentage of adults have persistent obstructive disease, both recognized and unrecognized.

Link HW: Pediatric asthma in a nutshell, Pediatr REV 35:287–297, 2014.
Sears MR, Greene JM, Willan AR, et al: A longitudinal, population-based, cohort study of childhood asthma followed to adulthood, N Engl J Med 349:1414–1422, 2003.

38. What diagnosis should be considered in a patient with poorly controlled asthma with recurrent infiltrates who has central bronchiectasis on a chest computed tomography (CT) scan and peripheral blood eosinophilia?
Allergic bronchopulmonary aspergillosis. This is a T-cell mediated hypersensitivity response to Aspergillus fumigatus (a ubiquitous fungus) that can cause migrating pulmonary infiltrates and central bronchiectasis. The condition occurs as a complication primarily in patients with asthma and cystic fibrosis. Diagnosis relies on an abnormal chest radiograph and CT scan, skin prick reactivity to A. fumigatus, elevated total serum IgE> 417 IU/L, and positive serum antibodies to A. fumigatus
(IgE and/or IgG).

Greenberger PA: Chapter 18: Allergic bronchopulmonary aspergillosis, Allergy Asthma Proc 33S: S61–S63, 2012.

BRONCHIOLITIS
39. What is the most important cause of lower respiratory tract disease among infants and young children?
Respiratory syncytial virus (RSV). Up to 100,000 children are hospitalized annually in the United States as a result of this pneumovirus, which is different from—but closely related to—the

paramyxoviruses. Disease most commonly occurs during outbreaks in winter or spring in the United States and during the winter months of July and August in the southern hemisphere. In the first 2 years of life, 90% of children will become infected with RSV, and up to 40% will develop some lower respiratory disease.

Hall CB, Weinberg GA, Iwane MK, et al: The burden of respiratory syncytial virus infection in young children,
N Engl J Med 360:588–598, 2009.

40. What other agents cause bronchiolitis?
RSV is estimated to cause 50% to 80% of cases. Other agents responsible for bronchiolitis include human metapneumovirus (second most common cause), parainfluenza virus, influenza virus types
A and B, and adenovirus. Of these, adenovirus is most likely to result in rare serious sequelae, such as obliterative bronchiolitis.

Teshome G, Gattu R, Brown R: Acute bronchiolitis, Pediatr Clin North Am 60:1019–1034, 2013.

41. What are the best predictors of the severity of bronchiolitis?
The single best predictor at an initial assessment appears to be oxygen saturation, which can be determined by pulse oximetry. An SaO2 of <95% correlates with more severe disease; a low SaO2 is often not clinically apparent, and objective measurements are necessary. An arterial blood gas with a PaO2 of 65 or less or a PaCO2 of >40 mm Hg is particularly worrisome. Other predictors of increased severity include the following:
• An ill or “toxic” appearance
• History of prematurity (gestational age <34 weeks)
• Atelectasis on chest radiograph
• Respiratory rate of >60 breaths/minute
• Infant <3 months old
42. What are the typical findings on a chest radiograph in a child with bronchiolitis?
The picture is varied. Most commonly, there is hyperinflation of the lungs. About 25% of
hospitalized infants have atelectasis or infiltrates. Bilateral interstitial abnormalities with peribronchial thickening are common, or patients may have lobar, segmental, or subsegmental consolidation that can mimic bacterial pneumonia. Bacteremia or secondary bacterial pneumonia, however, is unusual in patients with bronchiolitis. With the possible exception of atelectasis, the chest radiograph findings
do not correlate well with the severity of the disease.

43. Which patients with bronchiolitis are at risk for apnea?
Apnea in patients hospitalized with bronchiolitis has ranged from 3% to 7% in studies. Concerns
of apnea are often used as rationale for hospitalization. In one study, higher-risk patients were those born at term and <1 month, preterm infants (<37 weeks of gestation) and <48 weeks postconception, and those with an observed apneic episode before evaluation. If none of these clinical criteria were present, the risk of apnea was <1%. In another study, independent predictors of apnea were age
<2 weeks, birth weight <2.3 kg, reported apneic event during current illness, and preadmission oxygen saturation <90%.

Schroeder AR, Mansbach JM, Stevenson M, et al: Apnea in children hospitalized with bronchiolitis, Pediatrics 132: e1194-e1201, 2013.
Willwerth BM, Harper MB, Greenes DS: Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea, Ann Emerg Med 48:4441–4447, 2006.

44. Is the use of steroids justified for bronchiolitis?
Although corticosteroids have been used by clinicians for many years for the treatment of bronchiolitis, the preponderance of multiple controlled studies has shown no immediate or long-term advantage with their use, either by the systemic or inhaled route.

Schroeder AR, Mansbach JM: Recent evidence on the management of bronchiolitis, Curr Opin Pediatr 26: 328–333, 2014.

45. Is inhalation therapy effective for bronchiolitis?
Bronchodilators: The use of bronchodilator therapy for bronchiolitis is controversial, but in general, evidence has not supported significant efficacy. A 2010 meta-analysis found that outpatient use did not reduce the rate of hospitalization and that inpatient use did not shorten length of stay. Lack of benefit in bronchiolitis compared with asthma may be explained by the fact that bronchiolitis is characterized by bronchial wall edema and epithelial sloughing and not bronchospasm. Despite little support in
the literature of its value, bronchodilator therapy continues to be widely practiced.
Epinephrine: Some centers tout epinephrine, a therapy with α-agonistic vasoconstrictive properties, but recent evidence indicates no benefits compared with inhaled saline.
Hypertonic saline: In theory, hypertonic saline might be efficacious through the absorption of mucosal water in the bronchioles and enhancement of mucociliary clearance. Results of early clinical trials indicated some possible reduction in hospital length of stay, but multiple recent studies have demonstrated no benefit.

Schroeder AR, Mansbach JM: Recent evidence on the management of bronchiolitis, Curr Opin Pediatr 26:328–333, 2014. Jacobs JD, Foster M, Wan J, et al: 7% Hypertonic saline in acute bronchiolitis: a randomized controlled trial, Pediatrics 133: e8–e13, 2014.

46. Is there a vaccine to prevent RSV infection?
No, there is not yet a safe and effective vaccine against RSV, although vaccines are in development. Palivizumab (Synagis), a monoclonal antibody directed against RSV, is effective for prophylaxis of RSV infection in high-risk infants. It is given intramuscularly and must be given once per month during the RSV season. This drug is not indicated for the treatment of RSV infection.

47. Does infection with RSV confer lifelong protection?
No. In fact, reinfection is very common. In day care centers, up to 70% of infants who acquire RSV infections during the first year of life are reinfected during the subsequent 2 years. Primary infections tend to be the most severe episodes, with subsequent illnesses being milder. In older children and adults, RSV infections present with the same symptoms as “colds,” and reinfection is also common.
48. If a 5-month-old child is hospitalized as a result of RSV bronchiolitis, what should the parents be told about the likelihood of future episodes of wheezing?
In follow-up studies, 40% to 50% of these infants have subsequent recurrent episodes of wheezing, usually during the first year after illness. Subclinical pulmonary abnormalities may also persist.
The question of whether the pulmonary sequelae are the result of the bronchiolitis or of a genetic predisposition to wheezing or asthma remains unclear. Factors such as pulmonary abnormalities before the illness, passive cigarette smoke exposure, atopic diathesis, and immunologic responses of virus-specific IgE determine the risk for recurrence.

CLINICAL ISSUES
49. How is hemoptysis differentiated from hematemesis?
See Table 16-3.

Rosenstein BJ: Hemoptysis. In Hilman BC, editor: Pediatric Respiratory Disease, Philadelphia, 1993, WB Saunders, p 533.

Table 16-3. Hemoptysis Versus Hematemesis
HEMOPTYSIS HEMATEMESIS
Color Bright red and frothy Dark red or brown
pH Alkaline Acid
Consistency May be mixed with sputum May contain food particles
Symptoms Preceded by gurgling Accompanied by coughing Preceded by nausea Accompanied by retching

50. What are the indications for surgical repair of pectus excavatum?
This is still an area of considerable controversy. Nearly 1 in 400 children have this congenital chest wall anomaly. Children with pectus excavatum (Fig. 16-2) tend to have reduced total lung capacity, reduced vital capacity, increased residual volume, and reduced cardiac stroke volume during maximal exercise. However, most patients are still in the normal range for these values. The most common complaints relate to poor self-image and decreased exercise tolerance. Counseling is often sufficient for the cosmetic aspects, but many older patients report an improvement in exercise tolerance following repair, despite what appear to be minor changes in cardiac function. Whether
the reason is cosmetic or to improve maximal exercise, operative repair should be delayed until the child is >16 years of age to decrease the risk for recurrence during the pubertal growth spurt.

Obermeyer RJ, Goretsky MJ: Chest wall deformities in pediatric surgery, Surg Clin North Am 92:669–684, 2012.

Figure 16-2. Pectus excavatum. (From James EC, Corry RJ, Perry JF: Principles of Basic Surgical Practice. Philadelphia, 1987, Hanley & Belfus, p 173.)

51. What are the most common causes of chronic cough?
Postnasal drip and asthma. The differential diagnosis of chronic cough is very long and includes congenital anomalies, infectious or postinfectious cough, gastroesophageal reflux, aspiration, physical and chemical irritation, and psychogenic cough. After a thorough history and physical examination, evaluation with a chest radiograph and spirometry can also help establish the diagnosis.

Acosta R, Bahna SL: Chronic cough in children, Pediatr Ann 43:e176–e183, 2014.
Asilsoy S, Bayram E, Agin H, et al: Evaluation of chronic cough in children, Chest 134:1122–1128, 2008.

52. When should the diagnosis of psychogenic cough be considered?
A psychogenic cough should be considered in children with a persistent dry, honking, explosive daytime cough that disappears with sleep or at the weekend. It often starts after an upper respiratory infection (URI). The patient complains of a tickle or “something in the throat.” Physical examination and laboratory work are normal, and conventional therapies are ineffective. A behavioral approach with training in how to reduce the cough is the preferred treatment, although, in some cases, psychological intervention is required; hypnosis has also been employed successfully.

53. What medications are most effective for cold symptoms in children?
Multiple studies have failed to show benefit over placebo of any particular medication, including dextromethorphan, diphenhydramine, codeine, and echinacea. In addition, because the use of over-the- counter cold and cough products with antihistamines and decongestants have been implicated with many adverse events, a U.S. Food and Drug Administration advisory committee has recommended against their use in children <6 years of age. Many manufacturers have voluntarily removed such
products intended for children <2 years of age. Supportive care with patience and self-resolution
of symptoms (tincture of time) remain the mainstay of treatment.

Isbister GK, Prior F, Kilham HA: Restricting cough and cold medicines in children, J Paediatr Child Health 48:91–98, 2012.

54. Which is the more effective for cough in children: antihistamines, antitussives, mucolytics, decongestants, or honey?
Honey. Numerous studies have demonstrated that honey is a safe and effective treatment for cough associated with URI in children >1 year of age. Honey should not be given to children <1 year of age because of the risk of botulism. Since 2007, a number of advisory agencies, including the FDA, have cautioned against the use of over-the-counter cough and cold medications in children younger than 2 to 6 years of age because of a lack of proven efficacy and reported cases of misuse and
overdose with severe adverse clinical effects and deaths.

Mazer-Amirshahi M, Reid N, van de Anker J, Litovitz T: Effect of cough and cold medication restriction and label changes on pediatric ingestions reported to United States Poison Centers, J Pediatr 163:1372–1376, 2013 Cohen A, Rozen J, Kristal H, et al: Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study, Pediatrics 130:465–471, 2012

55. What constitutes passive cigarette smoke?
Passive cigarette smoke consists of both the smoker’s exhalation (mainstream smoke, about 15% of total) and the more noxious sidestream (the unfiltered burning end of the cigarette, about 85% of total).

56. What are the possible risks of passive cigarette smoke exposure?
• Decreased fetal growth and persistent adverse effects on lung function across childhood from smoking in pregnancy
• Increased incidence of sudden infant death syndrome
• Increased incidence of acute and chronic middle ear effusions
• Increased frequency of upper and lower respiratory tract infections
• Appearance of wheeze illness at an earlier age with more frequent exacerbations
• Impaired lung function during childhood from second-hand smoke after birth
Longer-term issues of increased cancer rates and cardiovascular disease remain under study.
In addition, if a parent smokes, a child is twice as likely to become a smoker.

U.S. Department of Health and Human Services: The Health Consequences of INVOLUntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Available at www.surgeongeneral.gov/library/reports/secondhandsmoke/ fullreport.pdf. Accessed on Jan. 13, 2015.

57. How is clubbing diagnosed? Digital clubbing is the presence of increased amounts of connective tissue under the base of the fingernail. This may be determined by the following:
• Rock the nail on its bed between the examiner’s finger and thumb. In patients with clubbing, the nail seems to be floating.
• Visual inspection reveals that the distal phalangeal depth (DPD), which is the distance from the top of the base of the nail to the finger pad, exceeds the interphalangeal depth (IPD), which is the distance from the top of the distal phalangeal joint to the underside of the joint. Normally, the DPD/IPD ratio is <1, but in patients with clubbing, it is >1.
• The diamond (or Schamroth) sign: Normally, if the nails of both index fingers or any other
two identical fingers are opposed, there is a diamond-shaped window present between the nail bases (Fig. 16-3); this window disappears in patients with clubbing.

Figure 16-3. A, Normal child with a diamond- shaped window between the nail bases when the fingers are opposed. B, In digital clubbing, the diamond-shaped window is obliterated by the increased amount of soft tissue under the base of the nail.

58. What are the causes of digital clubbing?
• Pulmonary: Bronchiectasis (as in cystic fibrosis, bronchiolitis obliterans, ciliary dyskinesia), pulmonary abscess, empyema, interstitial fibrosis, malignancy (bronchial carcinoma), pulmonary atrioventricular fistula
• Cardiac: Cyanotic congenital heart disease, chronic congestive heart failure, subacute bacterial endocarditis
• Hepatic: Biliary cirrhosis, biliary atresia, α1-antitrypsin deficiency
• Gastrointestinal: Crohn disease, ulcerative colitis, chronic amebic and bacillary diarrhea, polyposis coli, small bowel lymphoma
• Endocrine: Thyrotoxicosis, thyroid deficiency
• Hematologic: Thalassemia, congenital methemoglobinemia (rare)
• Idiopathic: May be a variation of normal and not indicative of underlying disease
• Hereditary: May be a variation of normal and not indicative of underlying disease

Modified from Hilman BC: Clinical assessment of pulmonary disease in infants and children. In Hilman BC, editor: Pediatric Respiratory Disease. Philadelphia, 1993, WB Saunders, p 61.

59. What is the pathophysiology of clubbing?
The answer is unclear. The increased connective tissue under the nail beds that causes digital clubbing may be caused by the presence of vasoactive substances that are increased because of hypoxia, increased production in chronic inflammatory disease, or decreased lung clearance. Possible mediators include platelet-derived growth factor and prostaglandin E2.
60. Nasal polyps are associated with which conditions?
Children: Nasal polyps are rare in children except as a manifestation of cystic fibrosis (Fig. 16-4). About 3% of children with cystic fibrosis have nasal polyps, which are often a recurrent problem that becomes more frequent with increasing age
• Adolescents: There is a wider range of possible diagnoses, including cystic fibrosis, allergic rhinitis, chronic sinusitis, malignancy, “triad asthma” (asthma, nasal polyps, aspirin sensitivity), and ciliary dyskinesia syndrome (e.g., Kartagener syndrome).

Figure 16-4. Nasal polyps in a patient with cystic fibrosis. (From Zitelli BJ, DAVIS HW: Atlas of Pediatric Physical Diagnosis, ed 4. St. Louis, 2002, Mosby, p 550.)

61. A patient with chronic sinusitis and recurrent pulmonary infections has a chest radiograph that demonstrates a right-sided cardiac silhouette. What diagnostic test should be considered next?
Bronchial or nasal turbinate mucosal biopsy for electron microscopic evaluation of cilia should be performed. Kartagener syndrome is one of the ciliary dyskinesia (or immotile cilia) syndromes. The presenting symptoms are a constellation of recurrent pulmonary infections, chronic sinusitis, recurrent otitis media, situs inversus, and infertility (in males). Structural ciliary abnormalities (most common are absent dynein arms) result in abnormal ciliary function and decreased clearance of respiratory secretions, thereby predisposing the patient to infection. In addition, because spermatozoa have tails with the same ultrastructural abnormalities as respiratory cilia, they move less well, causing infertility.
The cause of the situs inversus (Fig. 16-5) is not fully understood, but it occurs in about 50% of individuals with primary ciliary dyskinesia. It has been suggested that cilia are important for proper organ orientation during embryonic development and that dysfunctional cilia make organ orientation a random event, leading to situs inversus 50% of the time.

Figure 16-5. Dextrocardia with situs inversus. (From Clark DA: Atlas of Neonatology. Philadelphia, 2000, WB Saunders, p 115.)

62. What percentage of children snore?
Between 5% and 10% of preadolescent children are reported by their parents to snore at night.
63. In which children who snore should obstructive sleep apnea (OSA) be suspected? At night, the child with OSA may have persistent snoring interrupted by periods of silence during which respiratory efforts are made, but there is no air movement. Increased work of breathing, with retractions; prominent mouth breathing; unusual sleep postures; frequent nighttime awakenings; enuresis; and night sweats are symptoms of OSA. During the day, there may be excessive daytime sleepiness, learning problems, morning headaches, or personality changes. It’s estimated that 2% to 3% of the general pediatric population suffer from OSA; much higher rates are found in obese adolescents.

Reiter J, Rosen D: The diagnosis and management of common sleep disorders in adolescents, Curr Opin Pediatr 26:407– 412, 2014.

64. What evaluations should be performed on a child with suspected OSA?
• Physical examination is used to assess for mouth breathing while awake, midface or mandibular hypoplasia, tonsillar hypertrophy, cleft palate, palatal deformity caused by adenoidal hypertrophy, failure to thrive (FTT), or obesity.
• Lateral airway radiograph is one of the easiest and most direct means of assessing upper airway caliber. Less commonly required are CT or magnetic resonance imaging (MRI).

• Flexible nasopharyngoscopy is useful for dynamic assessment of the nasal cavities, upper airway, and larynx.
• Detailed nocturnal polysomnography (overnight sleep study or polysomnogram [PSG]) is the gold standard for the definitive diagnosis of OSA until consistent clinical correlates can be found.
• Cardiologic assessment (chest radiograph, electrocardiogram, and echocardiography) is used for children with documented OSA and severe or sustained oxygen desaturation.

Wetmore RF: Sleep-disordered breathing. In Wetmore RF, editor: Pediatric Otolaryngology: The Requisites, Philadelphia, 2007, Mosby Elsevier, pp 190–201.

65. What are the potential long-term consequences of OSA?
The most severe complications of OSA in children are right ventricular hypertrophy, hypertension, polycythemia, respiratory acidosis with compensatory metabolic alkalosis, life-threatening cor pulmonale, and respiratory failure. Later in life, OSA is associated with an increased risk for cardiovascular morbidity and mortality. It is strongly implicated in the development of hypertension, ischemic heart disease, arrhythmias, and sudden death (in individuals with coexisting ischemic heart disease);
it also contributes to the risk for stroke.

Capdevila OS, Kheirandish-Gozal L, Dayyat E, et al: Pediatric obstructive sleep apnea: complications, management, and long-term outcomes, Proc Am Thorac Soc 5:274–282, 2008.

66. What is the most common cause of infantile stridor?
Congenital laryngomalacia occurs as a result of prolapse of the poorly supported supraglottic structures—the arytenoids, the aryepiglottic folds, and the epiglottis—on inspiration (Fig. 16-6). Stridor is loudest after crying or exertion, but it typically does not interfere with feeding, sleep, or growth. Symptoms usually resolve by the time the infant is 18 months old.

Figure 16-6. Laryngomalacia. (A) Normal position of supraglottic structures during expiration. (B) Collapse of arytenoids during inspiration. (From Powitzky R, Stoner J, Fisher T, Digoy GP: Changes in sleep apnea after supraglottoplasty in infants with laryngomalacia, Int J Pediatr Otolaryngol 75:1234–1239, 2011.)

67. How can you clinically distinguish bilateral from unilateral vocal cord paralysis in an infant?
Normally, the vocal cords are tonically abducted, with voluntary adduction resulting in speech.
With unilateral paralysis, one cord is ineffective for speech, and hoarseness results. The infant’s cry may be weak or absent. Stridor is usually minimal but may be positional (e.g., sleeping on the side with the paralyzed cord up may allow it to fall to midline and produce obstructive sounds). With bilateral paralysis, hoarseness is less apparent, and the cry remains weak, but stridor (both inspiratory and expiratory) is usually quite prominent; in addition, the infant is more likely to have frank symptoms of pulmonary aspiration.

68. What is the most common cause of chronic hoarseness in children? Screamer’s nodes. These are vocal cord nodules caused by vocal abuse, such as repetitive screaming, yelling, and coughing. They are the cause of a hoarse voice in >50% of children
when hoarseness persists for >2 weeks.
69. What are the most common symptoms and signs in children with suspected foreign body aspiration?
Coughing and choking (witnessed or by history) occur in up to 80% to 90%, which highlights the importance of questioning about choking in a child who is evaluated for cough. The classic triad of cough, wheeze, and unilaterally decreased breath sounds is found in only about one third to one-half of patients.

Tan HKKK, Brown K, McGill T: Airway foreign bodies: a 10-year review, Int J Pediatr Otolaryngol 56:91–99, 2000.

70. Which other clinical features are suggestive of foreign-body aspiration?
Symptoms and history
• Child <4 years old
• Boys twice as common as girls
• Hemoptysis
• Respiratory infection not resolving with treatment
• Difficulty breathing
Signs
• Wheezing in a child who has no history of asthma
• Mediastinal shift
• One nipple higher than the other as a result of unilateral hyperinflation
• Stridor

71. Are chest radiographs useful for evaluating a foreign-body aspiration? Unfortunately, only about 10% to 20% of aspirated foreign bodies are radiopaque. Thus, inspiratory films are often normal. Features suggesting a foreign-body aspiration are as follows:
• Expiratory chest radiograph showing asymmetry in lung aeration as a result of obstructive emphysema (The foreign body often acts as a ball-valve mechanism, allowing air in but not out.) (Fig. 16-7)

Figure 16-7. Right-sided foreign body aspiration. Compared to inspiratory film (A), expiratory film (B) shows continued expansion on the right side due to air trapping caused by the foreign body. (From Pinzoni F, Boniotti C, Molinaro SM: Inhaled foreign bodies in pediatric patients: REVIEW of personal experience, Int J Pediatr Otolaryngol 71:1897–1903, 2007.)

• Right and left lateral decubitus films that show the same asymmetry (These views are often used in uncooperative children who cannot or will not exhale on command.)
• Local hyperinflation
• Obstructive atelectasis

72. On which side of the chest are foreign-body aspirations and aspiration pneumonias more common?
Right side, particularly in older children and adolescents. This occurs because of anatomic considerations. The right main stem bronchus, compared with the left, is wider, has a larger airflow, and has a less acute angle with the trachea. This allows for easier passage of both small foreign bodies or aspirated liquids to enter the right side and its secondary airways. This angulation difference is less pronounced in infancy and increases as children age through puberty. Thus, the younger the child, the less likely is a right-sided predominance.

73. What are the possible mechanisms for the development of lung abscesses in children?
• After pneumonia: Particularly Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, and Klebsiella pneumoniae
• Hematogenous spread: Especially if an indwelling central catheter or right-sided endocarditis is present
• Penetrating trauma
• Aspiration: Especially in neurologically compromised patients
• Secondary to infection of an underlying pulmonary anomaly: Such as a bronchogenic cyst

Campbell PW: Lung abscess. In Hilman BC, editor: Pediatric Respiratory Disease, Philadelphia, 1993, WB Saunders, pp 257–262.

74. What are the typical clinical findings in patients with bronchiectasis? Bronchiectasis is the progressive dilation of bronchi, most likely from acute and/or recurrent obstruction and infection. It may result from a variety of infections (e.g., adenoviral, rubeola, pertussis, tuberculosis), and it is often associated with underlying pulmonary susceptibility (e.g., cystic fibrosis, ciliary dyskinesia syndromes, immunodeficiencies). Clinical findings can be variable but usually include bad breath, persistent cough, chronic production of purulent sputum, recurrent fevers, and digital clubbing. Inspiratory crackles are often heard over the affected area. Hemoptysis and wheezing can occur but are uncommon.

75. A novice teenage mountain-climber develops headache, marked cough, and orthopnea at the end of a rapid 2-day climb. What is the likely diagnosis?
Acute mountain sickness with high-altitude pulmonary edema. This condition results from insufficient time to adapt to altitude changes above 2500 to 3000 meters, with alveolar and tissue hypoxia occurring as a result of pulmonary hypertension and pulmonary edema. In severe cases, cerebral edema can result. Treatment consists of returning the patient to a lower altitude and administering oxygen. If descent and supplemental oxygen are not available, portable hyperbaric chambers and nifedipine or phosphodiesterase-5 inhibitors should be used until descent is possible. If cerebral edema is suspected, dexamethasone is indicated.

Bärtsch P, Swenson ER: Acute high-altitude illnesses, N Engl J Med 368:2294–2302, 2013.

76. What is the likely diagnosis of a child with diffuse lung disease, microcytic anemia, and sputum that contains hemosiderin-laden macrophages?
Pulmonary hemosiderosis. This condition, the presenting symptoms of which can include chronic respiratory problems or acute hemoptysis, is characterized by alveolar hemorrhage and microcytic hypochromic anemia with a low serum iron level. Hemosiderin ingested by alveolar macrophages can often be detected in sputum or gastric aspirates after staining with Prussian blue. Most commonly, the condition is idiopathic and isolated, but it can be associated with cow milk hypersensitivity (Heiner syndrome), glomerulonephritis with anti–basement membrane
antibodies (Goodpasture syndrome), and collagen vascular disease.

77. How should a child with a spontaneous pneumothorax be managed?
If the pneumothorax is small and the child is asymptomatic, observation alone is appropriate. Administration of 100% oxygen may speed resorption of the free air, but this technique is less effective in children in older age groups. If the pneumothorax is larger than 20% (as measured by the [diameter of pneumothorax]3/[diameter of hemithorax]3) and/or the patient has evolving
respiratory symptoms, insertion of a thoracostomy tube and application of negative pressure should be considered. Signs of tension pneumothorax (e.g., marked dyspnea, tachypnea and tachycardia, unilateral thoracic hyperresonance with reduced breath sounds, tracheal shift) necessitate emergent aspiration and tube placement. Adolescents with spontaneous pneumothoraces have a high recurrence rate because of the common association with congenital subpleural blebs. As a follow-up measure, many authorities recommend chest CT with contrast because significant blebs can be treated thoracoscopically.
78. Describe the clinical and radiographic features of a tension pneumothorax
• Clinical: Increasing respiratory distress, hypoxemia, hypercarbia, hypotension
• Radiographic: Hyperlucency of the hemithorax, shifting of the mediastinum, flattening of the diaphragm, widening of the intercostal spaces (Fig. 16-8)

Figure 16-8. Tension pneumothorax. (From Katz DS, Math KR, Groskin SA, editors: Radiology Secrets. Philadelphia, 1998, Hanley & Belfus, p 61.)

79. What physical examination features suggest a pleural effusion?
• Dullness to percussion (“stony dullness”)
• Diminished or absent breath sounds on the side of the effusion
• Diminution in tactile fremitus
• Presence of a friction rub on auscultation
• Egophony (“e” to “a” changes)
80. In children with pleural effusions, how are exudates distinguished from transudates?
Exudative pleural effusions meet at least one of the following criteria:
• Pleural fluid protein–to–serum protein ratio of 0.5 or greater
• Pleural fluid lactate dehydrogenase (LDH)–to–serum LDH ratio of> 0.6
• Pleural fluid LDH concentration is >66% of the upper limit of normal for serum
If none of these criteria are met, the patient has a transudative pleural effusion. The criteria are
extremely sensitive for the identification of exudates, but specificity is much lower. Twenty percent of transudates from congestive heart failure may be incorrectly identified as exudates, particularly in the setting of diuretic use, which increases protein and LDH concentration in pleural fluid.

Muzumdar H: Pleural effusion, Pediatr REV 33:44-46, 2012.

81. What pediatric diseases are associated with exudative and transudative pleural effusions?
Exudates result from conditions of increased capillary permeability, whereas transudates occur with increased capillary hydrostatic pressure.
Exudative
• Pneumonia
• Tuberculosis
• Malignancy
• Chylothorax
Transudative
• Congestive heart failure
• Cirrhosis
• Nephrotic syndrome
• Upper airway obstruction
In children, the most common cause for a pleural effusion is pneumonia (“parapneumonic”), whereas, in adults, the most common etiology is congestive heart failure.

Beers SL, Abramo TJ: Pleural effusions, Pediatr Emerg Care 23:330–334, 2007.

82. What are possible treatments for infected parapneumonic effusions?
Although uncomplicated pleural effusions can usually be managed conservatively without the need for surgery, about 5% of patients with pleural effusions progress to empyema (Fig. 16-9). The precise approach to therapy is controversial and often varies by institution, but options include medical management alone or in combination with thoracentesis, chest tube drainage, video-assisted
thorascopic surgery (VATS) with chest tube drainage, intrapleural fibrinolytic therapy, and thoracotomy.
In general, a simple diagnostic and therapeutic thoracentesis is done with insertion of a chest tube in the early exudative phase of an empyema when fluid is accumulating. VATS therapy is more commonly the treatment of choice in early organizing empyemas (a fibrinopurulent phase), whereas thoracotomy, often combined with pleural stripping, is used in later, more advanced empyemas when scar formation can result in lung entrapment.

Shah SS, Hall M, Newland JG, et al: Comparative effectiveness of pleural drainage procedures for the treatment of complicated pneumonia in childhood, J Hosp Med 6:256–263, 2011.

Figure 16-9. Large left empyema with passive atelectasis of the adjacent lung. (From Chernick V, Boat TF, Wilmott RW, Bush A, editors: Kendig’s Disorders of the Respiratory Tract in Children, ed
7. Philadelphia, 2006, WB Saunders, p 374.)

83. What is the value of chest physiotherapy (CPT) in patients with pediatric pulmonary disease?
The main function of chest physiotherapy is to assist with the removal of tracheobronchial secretions to lessen obstruction, reduce airway resistance, enhance gas exchange, and reduce the work of breathing. A variety of techniques are used: chest wall percussion, vibration, and postural drainage. CPT has been advocated in patients with chronic sputum production (e.g., cystic fibrosis), primary pneumonia, and atelectasis; for intubated neonates; and for postextubation and postoperative patients. However, clinical benefits in each category—with the exception of diseases of chronic sputum production—remain highly anecdotal and understudied. Limited evidence does not support a role in bronchiolitis and asthma.

Chaves GS, Fregonezi GA, Dias FA, et al: Chest physiotherapy for pneumonia in children, Cochrane Database Syst REV 9: CD010277, 2013.
Roque I, Figuis M, Giné-Garriga M, et al: Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months, Cochrane Database Sys REV 2:CD004873, 2012.
American Association for Respiratory Care: www.aarc.org. Accessed on Jan. 13, 2015.

84. Who was Ondine, and what was her curse?
Ondine was a legendary water nymph who fell in love with Hans, a mortal. She put a curse on him with the stipulation that, should he ever betray her, he would suffocate by not breathing when he fell asleep. Unfortunately, Hans fell for the charms of Bertha, and he eventually succumbed to the curse while dozing. The term Ondine curse has been used to describe the syndrome of sleep apnea as a result of reduced respiratory drive, although the term central HYPOVENTILATION syndrome (CHS) is used more correctly. This rare condition is often associated with other abnormalities of brainstem
function. CHS can be idiopathic, or it can be a complication of an earlier insult to the developing brain. In some families, it is genetic. Children with CHS are initially treated by tracheostomy and mechanical ventilation during sleep. Results with phrenic nerve pacing have been good in older infants and children. Familial recurrence of CHS has suggested a genetic etiology and mutations in the PHOX2B gene have been reported in studies from France and the United States.

Marion TL, Bradshaw WT: Congenital central hypoventilation syndrome and the PHOX2B gene mutation, Neonatal Netw
30:397–401, 2011.

CYSTIC FIBROSIS
85. What is the basic defect in patients with cystic fibrosis (CF)?
Patients with CF have a defect in the CF transmembrane conductance regulator (CFTR) protein. This is a key ion channel that regulates chloride and sodium transfer across the apical membrane of epithelial cells and other cells. In patients with CF, chloride is poorly secreted into the lumen, and there is increased absorption of sodium from the luminal surface of the airway or duct, thereby resulting in respiratory and pancreatic secretions that are relatively dehydrated and viscid. These hyperviscous secretions obstruct pancreatic ducts, resulting in steatorrhea from exocrine pancreatic insufficiency, and they interfere with pulmonary mucociliary clearance, thereby causing chronic respiratory disease. In the sweat gland, CFTR is involved in the reabsorption of chloride, and abnormal CFTR function in patients with CF leads to the production of sweat with increased sodium and chloride concentrations. More than 1900 mutations of the gene that codes for this protein have been identified.

O’Sullivan BP, Freedman SD: Cystic fibrosis, Lancet 373:1891–1904, 2009.

86. What is the incidence of CF in various ethnic groups?
• Whites: 1 in 3300 live births
• Hispanics: 1 in 8000 to 9500 live births
• Native Americans (in the United States): 1 in 11,200 live births
• Blacks: 1 in 15,300 live births
• Asians: 1 in 32,100 live births

Cystic Fibrosis Foundation: www.cff.org. Accessed on Jan. 13, 2015.

87. What are the presenting signs and symptoms of CF?
These can be remembered with the acronym CF PANCREAS:
• Chronic cough and wheezing
• Failure to thrive
• Pancreatic insufficiency (signs of malabsorption, including bulky, foul stools)
• Alkalosis and hyponatremic dehydration
• Neonatal intestinal obstruction (meconium ileus) and Nasal polyps
• Clubbing of the fingers and Chest radiographs with changes
• Rectal prolapse
• Electrolyte elevation in sweat (salty skin)
• Absence or congenital atresia of the vas deferens
• Sputum with Staphylococcus or Pseudomonas (mucoid)

Schidlow DV: Cystic fibrosis. In Schidlow DV, Smith DS, editors: A Practical Guide to Pediatric Respiratory Diseases, Philadelphia, 1994, Hanley & Belfus, p 76.

88. How is the diagnosis of CF made?
The presence of one or more typical symptoms of CF, or a history of CF in a sibling, or an abnormal newborn screen plus laboratory evidence of CFTR dysfunction.
Laboratory evidence of CFTR dysfunction can be in the form of a positive sweat test, demonstration of 2 known disease-causing mutations or abnormal nasal potential difference measurements.

89. What constitutes an abnormal sweat test?
Sweat gland secretions should be obtained by pilocarpine iontophoresis. A level of sweat chloride
of >60 mEq/L is abnormal; 40 to 60 mEq/L is borderline; and <40 mEq/L is normal. Note that sweat chloride values <40 mEq/L have occasionally been demonstrated in genetically proven cases of CF. In infancy, values greater than 30 mEq/L should be considered abnormal and lead to further evaluation.

90. How are newborns screened for CF?
Newborns with CF have elevated levels of immunoreactive trypsinogen (IRT), a pancreatic enzyme precursor. If the initial screen for this compound is elevated (and sometimes a repeat IRT test to confirm elevation), mutational analysis of DNA or sweat testing is used to confirm the diagnosis. As of 2010, all states offer CF screening as part of their expanded newborn screening programs, and the sensitivity of the testing varies depending on the methodology and the reference ranges selected. In general, the testing is no more than 95% sensitive, so symptoms suggestive of CF in a child whose newborn screen was normal are an indication for sweat testing or mutational
analysis.

Wagener JS, Zemanick ET, Sontag MK: Newborn screening for cystic fibrosis, Curr Opin Pediatr 24:329–325, 2012.

91. When and why should children with cystic fibrosis be screened for possible CF-related diabetes mellitus?
Children with CF should be screened for possible CF-related diabetes mellitus after 9 years of age. Thick viscous secretions in CF patients cause obstructive damage to the exocrine pancreas, which ultimately can lead to islet cell destruction and diminishment of insulin production. Annual glucose tolerance testing is recommended after 9 years of age. The hemoglobin A1C test is not sufficient
as a screen because it underestimates glycemic control.

Paranjape SM, Mogayzel PJ Jr: Cystic fibrosis. Pediatr REV 35:194–204, 2014.

92. What are the mainstays of pulmonary therapy for children with CF?
• Airway clearance techniques (e.g., chest physiotherapy, mechanical vests, flutter valve)
• Mucolytic agents (e.g., recombinant human DNAse, hypertonic saline aerosols)
• Anti-inflammatory agents (e.g., ibuprofen, oral azithromycin)
• Bronchodilators (e.g., inhaled β2-agonists)
• Antibiotics (oral, inhaled, and intravenous)

O’Sullivan BP, Freedman SD: Cystic fibrosis, Lancet 373:1891–1904, 2009.

93. What is the role of Ivacaftor in the treatment of CF patients?
IVACAFTOR is an oral agent, classified as a CFTR potentiator that activates a defective CFTR at the cell surface in patients with a certain class III mutation (G551D). This mutation affects 4% to 5% of CF patients. Clinical trials involving patients with other mutations are underway. The resultant improvement in cellular channel function in airways increases chloride secretion, reduces excessive sodium and water absorption, and decreases secretion tenacity. However, it is one of the most expensive drugs ever marketed with a yearly cost in 2013 of over $300,000, which has prompted much criticism.

O’Sullivan B, Orenstein DM, Milla CE: Viewpoint: pricing for orphan drugs, will the market bear what society cannot?
JAMA 310:1343–1344, 2013.
Ramsey BW, Davies J, McElvaney NG, et al: VX09-770-102 Study Group. A CFTR potentiator in persons with cystic fibrosis and the G551D mutation. N Engl J Med 365:1663–1672, 2011.

94. Which features of CF have prognostic significance?
• Gender: Males have better survival rates than females, although the gap is narrowing.
• Colonization with virulent bacteria: Pseudomonas aeruginosa, methicillin-resistant
S. aureus (MRSA), and Burkholderia cepacia are more serious pathogens, which are often resistant to multiple drugs and difficult to clear after the patient becomes persistently infected. Stenotrophomonas maltophilia is an emerging problem; patients who are chronically colonized with these organisms have significantly poorer survival rates than other patients with CF.
• Diabetes mellitus is a negative prognostic factor that is associated with increased rates of decline in pulmonary function.
• Malnutrition is also associated with increased rates of decline in pulmonary function.
• Cor pulmonale is one of the late complications of CF because progressive obstructive airway disease leads to the development of pulmonary hypertension and respiratory failure. The patient’s prognosis is poor after the development of cor pulmonale.
• Pneumothorax is associated with moderate to advanced lung disease in patients with CF. Therefore, air leak has traditionally been regarded as a poor prognostic sign. The prognosis has been improving now that pneumothoraces are being managed aggressively.
• Worsening pulmonary function tests: Patients with an FEV1 level that is <30% of predicted have an increased 2-year mortality rate.

Montgomery GS, Howenstine M: Cystic fibrosis, Pediatr REV 30:302–309, 2009.
Kulich M, Rosenfeld M, Goss CH, Wilmott R: Improved survival among young patients with cystic fibrosis, J Pediatr
142:631–636, 2003.

PNEUMONIA
95. What agents cause pneumonia in children?
See Table 16-4.

Table 16-4. Agents That Cause Pneumonia
AGE VIRAL BACTERIAL ATYPICAL
Birth to 3 wk Cytomegalovirus Herpes simplex virus Group B streptococcus
Gram-negative enteric bacilli (e.g., Escherichia coli)
Listeria monocytogenes Ureaplasma urealyticum
3 wk to 3 mo Respiratory syncytial virus Streptococcus Chlamydia
Parainfluenza viruses pneumoniae trachomatis
Human metapneumovirus Bordetella pertussis
Influenza A and B Staphylococcus aureus
Adenovirus
Bocavirus
Rhinovirus
3 mo-5 yr Respiratory syncytial virus Streptococcus pneumoniae Mycoplasma
Parainfluenza viruses Haemophilus influenzae pneumoniae
Influenza A and B (nontypeable) Chlamydophila
Human metapneumovirus Staphylococcus aureus pneumoniae
Adenovirus
Bocavirus
Rhinovirus
5 yr to adolescence Influenza A and B Streptococcus pneumoniae Staphylococcus aureus Mycoplasma pneumoniae
Chlamydophila pneumoniae

96. What are important trends in the etiology of pneumonia in the United States?
• Bacterial: The introduction of the pneumococcal conjugate vaccines has substantially reduced hospitalizations for pneumonia.
• Viral: Viral pneumonia is more common in younger age groups, and most frequently is RSV. Human metapneumovirus, described initially in 2001, can mimic the clinical picture of RSV.
• Atypical pneumonia: Caused by Mycoplasma pneumoniae and Chlamydophila (formerly Chlamydia) pneumoniae, these infections were previously thought to be uncommon in preschool- age children. In this age group, the incidence is thought to be increasing. Both organisms become more prevalent in school-age children and are the most common etiology for pneumonia in older children.

Grijalva CG, Griffin MR, Nuorti JP, et al: Pneumonia hospitalizations among children before and after introduction of the pneumococcal conjugate vaccine—United States, 1997–2006. MMWR 58:1, 2009.

97. Are throat or nasopharyngeal cultures helpful for the diagnosis of pneumonia?
As a rule, the correlation between throat and nasopharyngeal bacterial cultures and lower respiratory tract pathogens is poor and of limited value. Healthy children may be colonized with a wide variety of potentially pathologic bacteria (e.g., S. aureus, nontypeable Haemophilus influenzae), which can be considered part of the normal flora; Bordetella pertussis is an exception. Polymerase chain reaction studies to identify respiratory viruses, C. pneumoniae, or M. pneumoniae are more useful because these organisms are much less commonly carried asymptomatically.
98. How often are blood cultures positive in children with suspected bacterial pneumonia? Blood cultures are positive 10% of the time or less in hospitalized patients. In outpatients with community- acquired pneumonia, the likelihood is significantly lower (<3%). Thus, the sicker the patient, the greater the potential yield. The incidence of bacteremia is unclear because the true denominator in
the equation (the number of true bacterial pneumonias) is difficult to ascertain because of the

imprecision with making a definitive diagnosis. The low rate of positive blood cultures does suggest that most bacterial pneumonias are not acquired by hematogenous spread.

Myers AL, Hall M, Williams DJ, et al: Prevalence of bacteremia in hospitalized pediatric patients with community-acquired pneumonia, Pediatr Infect Dis J 32:736–740, 2013.

99. How often are pleural fluid cultures positive in children with suspected bacterial pneumonia?
Between 60% and 85% are positive if antibiotics have not already been initiated. This high yield emphasizes the importance of recognizing a pleural effusion in patients with pneumonia and the value of early thoracentesis before starting antibiotic therapy.
100. Can a chest radiograph reliably distinguish between viral and bacterial pneumonia?
No. Viral infections more commonly have multifocal interstitial, perihilar, or peribronchial infiltrates; hyperinflation; segmental atelectasis; and hilar adenopathy. Effusions are uncommon. However, there can be considerable overlap in features with bacterial (and chlamydophilal and mycoplasmal) pneumonia. Bacterial pneumonia more commonly results in lobar and alveolar infiltrates, but the sensitivity and specificity of this finding are not very high.

Kronman MP, Shah SS: Pediatric community-acquired pneumonia, Contemp Pediatr 26:44–50, 2009.

101. What are indications for hospital admission in children with pneumonia?
• All who are toxic, dyspneic, or hypoxic
• Suspected staphylococcal pneumonia (e.g., pneumatocele on chest radiograph) (Fig. 16-10)
• Significant pleural effusion
• Suspected aspiration pneumonia (because of the higher likelihood of progression)
• Children who cannot tolerate oral medications or who are at significant risk for dehydration
• Suspected bacterial pneumonia in very young infants, especially with multilobar involvement
• Poor response to outpatient therapy after 48 hours
• Those whose family situation and chances for reliable follow-up are suboptimal

Figure 16-10. Pneumatocele after severe staphylococcal pneumonia (a thin-walled cyst in the right upper zone (arrow)). (From Adam A, Dixon AK, Gillard JH, et al: Grainger & Allison’s Diagnostic Radiology, ed 6. Philadelphia, 2015, ELSEVIER, p 1789.)

102. What clinical clues suggest atypical pneumonia?
Atypical pneumonia refers to one caused by certain bacteria, including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Characteristically, these infections start gradually, have minimal or a nonproductive cough, and have frequent constitutional signs
(e.g., headache, rash, and pharyngitis). Chest radiographs tend to show patchy, peribronchial infiltrates with only occasional lobar consolidation.
103. What are the causes of “afebrile infant pneumonia” syndrome?
The syndrome is usually the result of Chlamydia trachomatis, cytomegalovirus, Ureaplasma urealyticum, or Mycoplasma hominis. Affected infants develop progressive respiratory distress over several days to a few weeks, along with poor weight gain. A maternal history of a sexually transmitted infection is common. Chest radiographs reveal bilateral diffuse infiltrates with hyperinflation. There may be eosinophilia and elevated quantitative immunoglobulins (IgG, IgA, IgM). The etiologic causes overlap in the clinical picture, although a history of conjunctivitis suggests chlamydia.
104. What are the clinical characteristics of chlamydial pneumonia in infants?
• Illness occurs between 2 and 19 weeks after birth. Most infants show symptoms by 8 weeks of age.
• Onset is gradual, with upper respiratory prodromal symptoms lasting longer than 1 week.
• Nearly 100% of patients are afebrile.
• Less than half have inclusion conjunctivitis.
• Respiratory signs and symptoms include the following: staccato cough, tachypnea, diffuse crackles, and occasional wheezing.
• Chest radiograph reveals bilateral hyperexpansion and symmetric interstitial infiltrates.
• Seventy percent have an elevated absolute eosinophil count (>400/mm3).
• More than 90% have increased quantitative immunoglobulins.
105. How helpful are cold agglutinins in the diagnosis of M. pneumoniae infections? Cold agglutinins are IgM autoantibodies that are directed against the I antigen of erythrocytes, which agglutinate red blood cells at 4°C. Up to 75% of patients with mycoplasma infections will develop them, usually toward the end of the first week of illness, with a peak at 4 weeks. A titer of 1:64 supports the diagnosis. Other infectious agents, including adenovirus, cytomegalovirus, Epstein-Barr virus, influenza, rubella, Chlamydia, and Listeria, can also give a positive result.
A single cold agglutinin titer of 1:64 is therefore suggestive but not conclusive evidence of infection with M. pneumoniae. More definitive testing requires IgG and IgM serology (especially acute and convalescent titers), quantitative polymerase chain reaction (FQ-PCR) and culture.

Qu J, Wu J, Dong J, et al: Accuracy of IgM antibody testing, FQ-PCR and culture in laboratory diagnosis of acute infection by Mycoplasma pneumoniae in adults and adolescents with community-acquired pneumonia, BMC Infect Dis 13:172, 2013.

106. When do the radiologic findings of pneumonia resolve?
Although there is a wide range, as a rule, most infiltrates that result from S. pneumoniae resolve in 6 to 8 weeks, and those that are caused by RSV resolve in 2 to 3 weeks. However, with some viral infections (e.g., adenovirus), it may take up to 1 year for radiographs to normalize. If significant radiologic abnormalities persist for >6 weeks, there should be a high index of suspicion for a possible underlying problem (e.g., unusual infection, anatomic abnormality, immunologic
deficiency).

Regelmann WE: Diagnosing the cause of recurrent and persistent pneumonia in children, Pediatr Ann
22:561–568, 1993.

107. Do children with pneumonia need follow-up radiographs to verify resolution? Generally, no. Exceptions would include children with pleural effusions, those with persistent or recurrent signs and symptoms, and those with significant comorbid conditions (e.g., immunodeficiency).

Mahmood D, Vartzelis G, McQueen P, Perkin MR: Radiological follow-up of pediatric pneumonia: principle and practice, Clin Pediatr 46:160–162, 2007.

108. What are the causes of recurrent pneumonia?
• Aspiration susceptibility: Oropharyngeal incoordination, vocal cord paralysis, gastroesophageal reflux, tracheoesophageal fistula
• Immunodeficiency: Congenital, acquired
• Congenital cardiac defects: Atrial septal defect, ventricular septal defect, patent ductus arteriosus
• Abnormal secretions or reduced clearance of secretions: Asthma, cystic fibrosis, ciliary dyskinesia
• Pulmonary anomalies: Sequestration, cystic adenomatoid malformation
• Airway compression or obstruction: Foreign body, vascular ring, enlarged lymph node, malignancy
• Miscellaneous: For example, sickle cell disease, sarcoidosis

Brand PL, Hoving MF, de Groot EP: Evaluating the child with recurrent lower respiratory tract infections, Paediatr Respir REV 13:135–138, 2012.
Kaplan KA, Beierle EA, Faro A, et al: Recurrent pneumonia in children: a case report and approach to diagnosis, Clin Pediatr 45:15–22, 2006.

109. How does the pH of a substance affect the severity of disease in aspiration pneumonia?
A low pH is more harmful than a slightly alkaline or neutral pH, and it is more likely to be associated with bronchospasm and pneumonia. The most severe form of pneumonia is seen when gastric contents are aspirated; symptoms may develop in a matter of seconds. If the volume of aspirate is sufficiently large and the pH is <2.5, the mortality rate may exceed 70%. The radiographic picture may be that of an infiltrate or pulmonary edema. Unilateral pulmonary edema may occur if the child is lying on one side.
110. How should children with aspiration pneumonia be managed?
Acute aspiration can often be treated supportively without antibiotics because the initial process is a chemical pneumonitis. If secondary signs of infection occur, antibiotics should be started after appropriate cultures; either penicillin or clindamycin is a reasonable choice to cover the oropharyngeal anaerobes that predominate. If the aspiration is nosocomial, antibiotic coverage should be extended to include gram-negative organisms.

PULMONARY PRINCIPLES
111. In addition to underlying immunologic immaturity, why are infants more susceptible to an increased severity of respiratory disease?
• Very compliant chest wall (allows passage through birth canal but limits inspiratory effort as it distorts with increased respiratory loading)
• Respiratory muscles more easily fatigued as a result of decreased muscle mass and fewer type I muscle fibers (slow twitch, high oxidative fibers)
• Chest wall elastic recoil is low in infancy (airway closure occurs at a higher relative lung volume)
• High airway compliance facilitates airway collapse and air trapping
• Collateral ventilation poorly developed, thus increasing likelihood of atelectasis during illness
• Higher airway mucous gland concentration in infants than in adults
112. At what age do alveoli stop increasing in number?
Although extra-acinar airway development is complete by 16 weeks of gestation, alveolar multiplication continues after birth. Early studies suggested that postnatal alveolar multiplication

ends at 8 years of age. However, more recent studies have shown that it is terminated by
2 years of age and possibly between 1 and 2 years of age. After the end of alveolar multiplication, the alveoli continue to increase in size until thoracic growth is completed.
113. What is the normal respiratory rate in otherwise healthy children?
Rates in children who are awake can be widely variable, depending on their psychological state and activity. Rates while sleeping are much more reliable and are a good indicator of pulmonary health. As a general rule in an afebrile, otherwise healthy and calm, resting infant or child, the expected maximal respiratory rate declines with increasing age. In the absence of other signs and symptoms, term newborns breathe up to a mean of 50 breaths/minute, decreasing to 40 breaths/ minute by 6 months and to 30 breaths/minute at 1 year. Beyond 1 year of age, the rate declines gradually, reaching the typical adult rate of 14 to 20 breaths/minute by the middle teenage years. Counting respiratory rates over 1 minute gives a more accurate measurement than extrapolating rates over shorter periods to 1 minute.
114. What is the significance of grunting respirations?
Grunting respirations are crying-like noises heard during expiration and are thought to be a physiologic attempt to maintain alveolar patency (PEEP). In patients seen in hospital settings, grunting is associated with a higher likelihood of serious infections, including pneumonia, pyelonephritis, and peritonitis.

Bilavsky E, Shouval DS, Yarden-Bilavsky H, et al: Are grunting respirations a sign of serious bacterial infection in children? Acta Paediatr 97:1086–1089, 2008.

115. What is normal oxygen saturation in healthy infants who are <6 months?
In a longitudinal study using pulse oximetry, baseline saturation was higher than 95% (normal
was 98%, with the lower 10th percentile at 95%). However, acute desaturations are common; almost all are associated with brief episodes of apnea while sleeping.

Hunt CE, Corwin MJ, Lister G, et al: Longitudinal assessment of hemoglobin saturation in healthy infants during the first six months of life, J Pediatr 134:580–586, 1999.

116. What is the difference among Kussmaul, Cheyne-Stokes, and Biot types of breathing patterns?
• Kussmaul: Deep, slow, regular respirations with prolonged exhalation; seen in diabetic ketoacidosis and salicylate ingestion
• Cheyne-Stokes: Crescendo-decrescendo respirations alternating with periods of apnea (no breathing); causes include heart failure, uremia, central nervous system trauma, increased intracranial pressure, and coma
• Biot (also known as ataxic breathing): Characterized by unpredictable irregularity; breaths may be shallow or deep and stop for short periods; causes include respiratory depression, meningitis, encephalitis, and central nervous system lesions involving the respiratory centers
117. Why a sigh?
A sigh is just a sigh in Casablanca, but it is also a very effective anti-atelectatic maneuver. By definition, it is a breath that is more than three times the normal tidal volume.
118. Is there a respiratory basis for yawning?
Although a respiratory function for yawning is frequently suggested, scientific support for this belief is minimal. Increasing the concentration of CO2 in inspired air increases the respiratory rate but does not change the rate of yawning. Relief of hypoxia and opening areas of microatelectasis are other theories that are not supported by scientific studies. Some authors hypothesize that yawning may be an arousal reflex.
119. At what concentration is inspired oxygen toxic? In addition to atelectasis, high oxygen concentration can cause alveolar injury with edema, inflammation, fibrin deposition, and hyalinization. The precise level of hyperoxia that results in injury is unclear and varies by age and underlying lung pathology, but a reasonable rule is to assume that a concentration

of more than 80% for longer than 36 hours is likely to result in significant ongoing damage; 60% to 80% is likely to be associated with more slowly progressive injury. An inspired oxygen concentration of 50%, even when administered for extended periods of time, is unlikely to cause pulmonary toxicity.

Jenkinson SG: Oxygen toxicity, J INTENSIVE Care Med 3:137–152, 1988.

120. Why is a child who is receiving 100% oxygen more likely to develop atelectasis than one who is breathing room air?
Nitrogen is more slowly absorbed than oxygen by alveoli. In room air (with its 78% nitrogen), alveolar collapse is minimized by the continued presence and pressure of nitrogen gas (the “nitrogen stint”). With 100% oxygen breathing, however, the high solubility of oxygen in blood can lead to absorption atelectasis in areas of poor ventilation and intrapulmonary shunting.
121. At what PaO2 does cyanosis develop? Cyanosis develops when the concentration of desaturated (i.e., reduced) hemoglobin is at least 3 gm/dL centrally or 4 to 6 g/dL peripherally. However, multiple factors affect the likelihood that a given PaO2 will result in clinically apparent cyanosis: anemia (less likely), polycythemia (more likely), reduced systemic perfusion or cardiac output (more likely), and hypothermia (more likely). Cyanosis is generally a sign of significant hypoxia. In a patient with adequate perfusion and a normal hemoglobin, central cyanosis is commonly noted when the PaO2 is about 50 mm Hg.
122. What are the causes of a reduced PaO2 associated with an increased A-aDO2 (alveolar-arterial oxygen tension difference or A-a gradient)?
• Right-to-left shunting: Intracardiac, abnormal arteriovenous connections; intrapulmonary shunts that result from perfusion of airless alveoli (e.g., pneumonia, atelectasis), often referred to as ventilation-perfusion mismatching
• Maldistribution of ventilation: Asthma, bronchiolitis, atelectasis, and so forth
• Impaired diffusion: An uncommon mechanism because many of the conditions previously thought to have a “diffusion block” (e.g., respiratory distress syndrome) also have a major component of shunting; may be seen when interstitial edema affects the septal walls (e.g., in early pulmonary edema and interstitial pneumonia)
• Decreased central venous oxygen content: As a result of a sluggish circulation (e.g., shock) or increased tissue oxygen demands (e.g., sepsis)
123. How does the pulse oximeter work?
The key principle behind pulse oximetry is that oxygenated hemoglobin allows for more transmission of certain wavelengths of red light than does reduced hemoglobin. By contrast, transmission of infrared light is unaffected by the amount of oxyhemoglobin present. A light source of red and infrared wavelengths is applied to an area of the body thin enough that the light can traverse a pulsating capillary bed and be detected by a light detector on the other side. Each
pulsation increases the distance the light has to travel, which increases the amount of light absorption.
A microprocessor derives the arterial oxygen saturation by comparing absorbencies at baseline and during the peak of a transmitted pulse.

Sinha I, Magell SJ, Halfhide C: Pulse oximetry in children, Arch Dis Child Educ Pract Ed 99:117–118, 2014.

124. What are the disadvantages or limitations of pulse oximetry?
• Patient movement disturbs measurements.
• Poor perfusion states affect accuracy.
• Fluorescent or high-intensity light can interfere with results.
• It is unreliable if abnormal hemoglobin is present (e.g., methemoglobin).
• It is unable to detect hypoxia until the PaO2 decreases below 80 mm Hg.
• Accuracy diminishes with arterial saturations below 70% to 80%.
125. In infants with unilateral lung disease, should the good lung be up or down?
The good lung should be up. This is another example of why children are not simply small adults. It is well established that adults with unilateral lung disease treated in a decubitus position will have an

increase in oxygen saturation when the good lung is placed down; this occurs because of an increase in ventilation to the dependent lung. Studies have shown that the opposite occurs in infants and children because ventilation is preferentially distributed toward the uppermost lung. This positional redistribution of ventilation appears to change to an adult pattern during the late teenage years.

Davies H, Helms P, Gordon I: Effect of posture on regional ventilation in children, Pediatr Pulmonol 12:227–232, 1992.

Acknowledgment
The editors gratefully acknowledge contributions by Drs. Ellen R. Kaplan, Carlos R. Perez, William D. Hardie, Barbara A. Chini, and Cori L. Daines that were retained from the first three editions of Pediatric Secrets.

BONUS QUESTIONS
126. How can house dust mite (HDM) concentrations be minimized?
Allergens from HDMs are among the most common triggers for allergic rhinitis and asthma. They are found throughout homes, but accumulate in bedding, soft furnishings, and carpet. HDM allergen reduction methods include the following:
• Encasing pillows, mattresses, and box springs in allergen-proof, zippered covers. While not effective as a single measure, there is evidence these covers may be of benefit when used as part of an extensive bedroom based dust mite allergen reduction program.
• Bedding may be washed in hot (55 °C [131 °F]) water. Drying the bedding in high heat in a dryer is an alternative that may prevent scalding injuries in children from having the water heater temperature raised above 50 °C (120 °F).
• Humidity should be reduced indoors to <45% using a dehumidifier and/or air conditioning with the windows closed.
• Wall-to-wall carpeting should be removed as much as possible and replaced with throw rugs. These should be regularly washed or dry-cleaned.

Sheikh A, Hurwitz B, Nurmatov U, et al: House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD001563.
Wood RA: Environmental control. In Leung DYM, Sampson HA, Geha RS, Szefler SJ, editors: Pediatric Allergy: Principles and Practice, St. Louis, 2003, Mosby, p 270.

127. Is a nebulizer more effective than a metered-dose inhaler (MDI) with a spacer for the treatment of asthma?
For the treatment of exacerbations of asthma, nebulizers are primarily used in children <2 years of age because of the ease of administration. Although an MDI with a spacer is used more commonly among older children, several studies in emergency rooms indicate that they are equally or more
effective than nebulizers among young children, even those with moderate or severe acute asthma.
Furthermore, the MDI with a spacer requires less treatment time and has fewer side effects, and it is often preferred by patients and parents.

Dolovich MB, Ahrens RC, Hess DR, et al: Device selection and outcomes of aerosol therapy: evidence based guidelines,
Chest 127:335–371, 2005.
Castro-Rodriguez JA, Rodrigo GJ: Beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis, J Pediatr 145:776–779, 2004.