Chapter 19: Respiratory Tract & Mediastinum

Pediatric pulmonary diseases account for almost 50% of deaths in children younger than 1 year and about 20% of all hospitalizations of children younger than 15 years. Approximately 7% of children have a chronic disorder of the lower respiratory system. Understanding the pathophysiology of many pediatric pulmonary diseases requires an appreciation of the normal growth and development of the lung.

Normal fetal lung development progresses through five stages with considerable overlap in the timing of each stage (Table 19–1). Interruption of the sequence leads to significant neonatal pulmonary difficulties that may extend lifelong. The normal human term newborn infant does not have a full complement of alveoli at birth, usually 100–150 million; this will increase with normal growth to the adult number of 300–600 alveoli. Infants who miss even the last few weeks of gestation may be challenged to meet the demands of transition from fetal life to air breathing due to incomplete alveolarization, and this may be accentuated by additional stress such as higher altitude or infection

PHYSICAL EXAMINATION OF THE RESPIRATORY TRACT

The complete pulmonary examination includes inspection, palpation, auscultation, and percussion. Inspection of respiratory rate and work of breathing is critical to the detection of pulmonary disease. Tachypnea, abnormalities of attentiveness, inconsolability, increased respiratory effort, color, and movement are reliable signs of hypoxemia. Palpation of tracheal position, symmetry of chest wall movement, and vibration with vocalization can help in identifying intrathoracic abnormalities. For example, a shift in tracheal position from midline can suggest pneumothorax or significant unilateral atelectasis. Tactile fremitus may change with consolidation or air in the pleural space. Auscultation should assess the intensity and symmetry of breath sounds and the presence of abnormal sounds such as fine or coarse crackles, wheezing, or rhonchi. Wheezing or prolonged expiratory compared to inspiratory time suggests intrathoracic airways obstruction. Tachypnea with an equal inspiratory and expiratory time suggests decreased lung compliance. It is important to know the lung anatomy in order to identify the location of abnormal findings (Figure 19–1). In older patients, unilateral crackles are the most valuable examination finding in pneumonia. Percussion may identify tympanic or dull sounds that can help define an effusion or pneumothorax. This component of the examination can prove challenging in young children.

Extrapulmonary manifestations of pulmonary disease include acute findings such as cyanosis and altered mental status; and signs of chronic respiratory insufficiency including growth failure, clubbing, and osteoarthropathy. Evidence of cor pulmonale (loud pulmonic component of the second heart sound, hepatomegaly, elevated neck veins, and rarely, peripheral edema) signifies pulmonary hypertension and may accompany advanced lung disease.

Respiratory disorders can be secondary to disease in other systems. It is therefore important to look for other conditions such as fever, metabolic acidosis, congenital heart disease, neuromuscular disease, immunodeficiency, autoimmune disease, and occult malignancy. Children with an elevated body mass index are more likely to present with sleep or respiratory symptoms and need to be evaluated for pulmonary pathology versus deconditioning or dyspnea.

PULMONARY FUNCTION TESTS

Pulmonary function tests (PFTs) are objective measures of pulmonary physiology that can differentiate obstructive from restrictive lung diseases, measure disease progression, and evaluate response to therapy. Because the normal values change with growth, serial determinations of lung function are often more informative than a single determination. Patient cooperation and consistent effort is essential for almost all standard PFTs. Most children aged 5 and older can perform pulmonary function testing. Younger children may be able to produce reliable results with coaching and visual incentives. Children with cystic fibrosis (CF) and asthma should perform pulmonary function testing routinely as early as they can cooperate. The values measured include forced vital capacity (FVC), which is the total volume of air that is exhaled; forced expiratory volume in the first second of the exhalation (FEV₁); the ratio of the FEV₁/FVC; forced expiratory flow at the middle of the vital capacity (FEF_25–75); and peak expiratory flow rate (PEFR). With a more robust sample of normal subjects, reference equations are now available from age 4 to 80, and the lower limit of normal is defined by a Z-score of 1.64. Commonly seen obstructive lung processes include asthma, bronchopulmonary dysplasia (BPD), and (CF). Common restrictive lung diseases include chest wall deformities, muscle weakness, and interstitial lung diseases (ILDs). Confirmation of restrictive lung physiology requires lung volume measurements (eg, total lung capacity, residual volume, and functional residual capacity) with special equipment. (For examples of PFTs, see Figures 19–2, 19–3, 19–4.)

PEFR, the maximal flow recorded during an FVC maneuver, can be assessed by handheld devices. These devices are not as well calibrated as spirometers, and the PEFR measurement can vary greatly with patient effort, so they are not good substitutes for actual spirometry. However, peak flow monitoring can be helpful in a patient with asthma that is difficult to control or for patients with poor perception of their airflow obstruction.

ASSESSMENT OF OXYGENATION & VENTILATION

Arterial blood gas measurements define the acid-base balance between respiration in the tissue and in the lungs. Blood gas measurements evaluate hypoxemia, acidosis, and hypercarbia and can be used to categorize acid-base disturbances as respiratory, metabolic, or mixed. Blood gas measurements are affected by abnormalities of ventilation/perfusion (V̇/Q̇) matching, respiratory control, ventilation, and respiratory mechanics. In pediatrics, hypoxemia (low partial pressure of arterial oxygen [PaO₂]) most commonly results from ventilation (V̇) and perfusion (Q̇) mismatch. Common pediatric diseases associated with hypoxemia due to V̇/Q̇ mismatch include acute asthma, CF, pneumonia, bronchiolitis, and BPD. Other causes of hypoxemia include hypoventilation, shunts (physiologic and anatomic), and diffusion barrier for oxygen. Hypercapnia (elevated partial pressure of arterial carbon dioxide [PaCO₂]) results from hypoventilation (ie, inability to clear the CO₂ produced). Causes include decreased central respiratory drive, respiratory muscle weakness, and low-tidal-volume breathing as seen in restrictive lung or chest wall diseases. Hypercapnea can also occur when severe V̇/Q̇ mismatch is present, which may occur with severe CF or BPD. Table 19–2 gives normal values for arterial pH, PaO₂, and PaCO₂ at sea level and at 5000 ft.

Venous blood gas analysis or capillary blood gas analysis can be useful for the assessment of PCO₂ and pH, but not PO₂ or saturation. Noninvasive assessment of oxygenation can be achieved with pulse oximetry (SpO₂). Values of SpO₂ are reliable as low as 80%. Reliability is reduced with poor arterial pulsation (eg, with hypothermia, hypotension, or infusion of vasoconstriction). Carbon monoxide bound to hemoglobin results in falsely high SpO₂ readings. Exhaled or end-tidal CO₂ monitoring can be used to noninvasively estimate arterial CO₂ content. It is used to monitor alveolar ventilation and is most accurate in patients without significant lung disease, particularly those good V̇/Q̇ matching and without airway obstruction. Monitoring of exhaled or end-tidal CO₂ is commonly used during polysomnogram (PSG) and anesthesia. Transcutaneous PCO₂ monitoring is also feasible but may be less reliable than transcutaneous PO₂ monitoring and should be used with caution.

DIAGNOSIS OF RESPIRATORY TRACT INFECTIONS

Respiratory tract infections may be caused by bacteria, viruses, atypical bacteria (eg, Mycoplasma pneumoniae and Chlamydia pneumoniae), Mycobacterium tuberculosis, nontuberculous mycobacterium, or fungi (eg, Aspergillus and Pneumocystis jiroveci). The type of infection suspected and appropriate diagnostic tests vary depending on factors such as underlying lung disease, immune function, and geographic region. Sources of respiratory tract secretions for diagnostic testing include nasopharyngeal and oropharyngeal swabs; expectorated and induced sputum; tracheal aspirates; direct lung or pleural fluid sampling; bronchoalveolar lavage (BAL) fluid; and gastric aspirates, specifically for M tuberculosis. Spontaneously expectorated sputum is the least invasive way to collect a sample for diagnostics, though it is rarely available from patients younger than 6 years. Sputum induction, performed by inhaling aerosolized hypertonic saline, is a relatively safe, noninvasive means of obtaining lower airway secretions. Sputum induction has been used in patients with CF and may be useful in patients with suspected M tuberculosis, P jiroveci pneumonia, or complicated community-acquired pneumonia (CAP). Tracheal aspirates can be obtained easily from patients with endotracheal or tracheostomy tubes. Culture of respiratory tract samples is the most commonly used approach to detect and identify airway pathogens. Molecular diagnostic tests, based on polymerase chain reaction (PCR) amplification and detection of nucleic acid from microbes, are often more rapid and sensitive, and may be used for detection of typical bacterial pathogens (eg, Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus), as well as detection of M tuberculosis, P jiroveci, and fastidious bacteria such as anaerobes. Blood and urine samples also may be used for serologic and antigen testing.

IMAGING OF THE RESPIRATORY TRACT

The plain chest radiograph remains the foundation for investigating the pediatric thorax. Both frontal (posterior-anterior) and lateral views should be obtained if feasible. The radiograph is useful for evaluating chest wall abnormalities, heart size and shape, mediastinum, diaphragm, airways, and lung parenchyma. When pleural fluid is suspected, lateral decubitus radiographs may be helpful in determining the extent and mobility of the fluid. When a foreign body is suspected, forced expiratory radiographs may show focal air trapping and shift of the mediastinum to the contralateral side. Lateral neck radiographs can be useful in assessing the size of adenoids and tonsils and also in differentiating croup from epiglottitis, the latter being associated with the “thumbprint” sign.

Fluoroscopic studies including upper gastrointestinal (UGI) series, esophagram, or videofluoroscopic swallow studies (VFSS) are indicated for detection of swallowing dysfunction in patients with suspected aspiration, tracheoesophageal fistula, vascular rings and slings, and achalasia. Fluoroscopy or ultrasound of the diaphragm can detect paralysis by demonstrating paradoxic movement of the involved hemidiaphragm.

Volumetric chest CT is recommended for evaluation of congenital lung lesions, pleural disease (eg, effusion or recurrent pneumothorax), complicated pneumonia, mediastinal disorders (eg, lymphadenopathy), interstial lung disease (ILD) and bronchiectasis. The addition of contrast may be needed to evaluate masses and nodules and CT angiography to delineate vasculature. Magnetic resonance imaging (MRI) is also useful for defining vascular or bronchial anatomical abnormalities. Concerns about radiation exposure in children led to the Image Gently campaign, an initiative of The Alliance for Radiation Safety in Pediatric Imaging, dedicated to increasing awareness of the need for radiation protection for children. Identified challenges include the need for continued education particularly at adult-focused hospitals, increased emphasis on appropriateness of pediatric imaging and research to validate CT outcomes, and establishing ranges of optimal CT technique when imaging children.

LARYNGOSCOPY & BRONCHOSCOPY

Direct visualization of the airways may be necessary for diagnosis despite an extensive history and physical and sophisticated imaging. This can be achieved with rigid or flexible instrumentation. Indications for laryngoscopy include hoarseness, stridor, symptoms of obstructive sleep apnea (OSA), and laryngeal wheezing. Indications for bronchoscopy include wheezing, suspected foreign body, suspected tracheoesophageal fistula, recurrent pneumonia, persistent atelectasis, chronic cough, and hemoptysis. A flexible bronchoscope can also be used to assess placement and patency of an endotracheal tube. In general, the more specific the indication, the higher the diagnostic yield. Rigid and flexible bronchoscopes have individual advantages, and for some patients, both should be employed sequentially under the same anesthesia.

The rigid, open tube instruments have the best optics and allow surgical intervention to be easily achieved, such as removal of a foreign body. Flexible laryngoscopes and bronchoscopes are of a smaller caliber, and therefore do not stent the airway open during the procedure. Dynamic airway collapse is better evaluated by flexible bronchoscopy, and more distal airways can be evaluated better with the flexible scope than with the rigid scope. In fiberoptic endoscopic evaluation of swallowing (FEES), a laryngoscope is used to visualize the larynx while the patient swallows liquids or food that has been dyed blue or green. BAL is useful to sample the alveolar space for infection, inflammation, or hemorrhage. Although removal of foreign bodies has been achieved with the flexible bronchoscope in larger children, the standard of care in most institutions is to remove foreign bodies via the rigid bronchoscope. Rigid bronchoscopy is done with general anesthesia. Flexible laryngoscopy may be performed awake. Flexible bronchoscopy is typically performed in children with general anesthesia, although can be performed with less sedation, especially through a tracheostomy tube.

Transbronchial biopsy in children is limited to evaluation of infection and rejection in lung transplant patients. There is low diagnostic yield in most other conditions. Transbronchial biopsy may have a role in sarcoidosis. Video-assisted thoracoscopic lung surgery (VATS) provides a more substantial specimen for pathologic assessment.

OXYGEN THERAPY

Oxygenation can be measured by the arterial oxygen tension or pulse oximetry (SpO₂). The advantages of the latter noninvasive method include obtaining continuous measurements during normal activities and avoiding artifacts caused by crying or breath-holding during arterial or venous puncture. For children with cardiopulmonary disorders that require chronic supplemental oxygen therapy (eg, BPD or CF), frequent noninvasive assessments are essential to ensure the safety and adequacy of oxygenation.

Supplemental oxygen (O₂) therapy is used to relieve hypoxemia, and the benefits may include reducing the work of breathing, reducing respiratory symptoms, relaxing the pulmonary vasculature, and improving feeding tolerance. Patients breathing spontaneously can receive supplemental O₂ via nasal cannula, head hood, or mask (including simple, rebreathing, nonrebreathing, or Venturi masks). The goal of O₂ therapy is to achieve an arterial oxygen tension of 65–90 mm Hg or SpO₂ above 90%. Lower PaO₂ or SpO₂ levels may be acceptable in certain situations, particularly cyanotic congenital heart disease. The actual O₂ concentration achieved by nasal cannula or mask depends on the flow rate, the type of mask used, and the patient’s age. Small changes in flow rate during O₂ administration by nasal cannula can lead to substantial changes in inspired oxygen concentration in young infants. The amount of oxygen required to correct hypoxemia may vary with activity; for example, an infant with chronic lung disease who uses 0.25 L/min while awake may need 0.5 L/min while asleep or feeding.

Head hood O₂ delivery is not often used if the patient can use a nasal cannula, which allows more mobility. Even at high flow rates, O₂ by nasal cannula rarely delivers inspired oxygen concentrations greater than 40%–45%. In contrast, partial rebreathing and nonrebreathing masks or head hoods can achieve inspired oxygen concentrations as high as 90%–100%. Heated humidified high-flow nasal cannula delivery allows a much higher high flow rate and is used with increasing frequency when standard low flow supplemental O₂ is not meeting SpO₂ goals.

INHALATION OF MEDICATIONS

Inhalation of medications is a mainstay of therapy for pediatric respiratory conditions and are routinely used CF, BPD, and asthma, as well as in acute illnesses such as infectious laryngotracheobronchitis and bronchiolitis (Table 19–3). Short-acting β-agonists and anticholinergics provide acute bronchodilitation (relievers), whereas inhaled corticosteroids and cromones provide anti-inflammatory effects (controllers). Nebulized antibiotics have documented benefit in CF and nebulized mucolytic medications (eg, rhDNAse and hypertonic saline) are used in CF and other conditions with impaired secretion control such as non-CF bronchiectasis.

The medications can be delivered by pressurized metered dose inhaler (pMDI), dry powder inhaler (DPI), or compressed air-driven wet nebulization. Careful attention to delivery technique is critical to optimize medication delivery to the airways. A valved holding chamber or similar spacer should be used with pMDI use, and this technique has been shown to be effective in infants as young as 4 months of age. A face-mask interface is recommended for both pMDI and wet nebulization in infants and toddlers; a simple mouth piece suffices for older children who can form a seal around the mouthpiece. Delivery technique should be assessed and reviewed at each clinical visit.

AIRWAY CLEARANCE THERAPY

Airway clearance is the mobilization and expulsion of airway secretions or debris. Innate airway clearance comprises mucociliary clearance and cough. Airway clearance therapies intend to reproduce or augment these functions. Currently available airway clearance techniques include: manual percussion or chest physiotherapy, postural drainage, forced expiratory technique (huff cough), autogenic drainage, positive expiratory pressure with handheld devices, intermittent positive pressure breathing, high-frequency chest wall oscillation or compression, intrapulmonary percussive ventilation, and manual or mechanical insufflation-exsufflation. All the above except insufflation-exsufflation techniques have been used in CF, bronchiectasis, and tracheobronchomalacia due to impaired mucociliary function. Often, therapies are combined (eg, high-frequency chest wall compression plus huff cough) to maximize the effect. Insufflation-exsufflation (commonly called cough assist) is used when cough force is weakened as in neuromuscular diseases, neurologic injury, or prolonged immobility. The decision about which technique to use should be based on the patient’s underlying airway clearance impairment, age, preference, and ability to participate. Bronchodilators or mucolytic medications may be given prior to or during airway clearance therapy. If prescribed, inhaled corticosteroids and inhaled antibiotics should be given after airway clearance therapy so that the airways are first cleared of secretions, allowing the medications to maximally penetrate the lung. Airway clearance has not been shown to be beneficial for patients with acute respiratory illnesses such as pneumonia, bronchiolitis, and asthma. Contraindications to airway clearance therapy include retained foreign body, hemoptysis, untreated pneumothorax, chest trauma, recent airway or open chest surgery, and concerns for increased intracranial pressure. Daily exercise is an important adjunctive therapy for airway clearance and overall lung health.

AVOIDANCE OF ENVIRONMENTAL HAZARDS

Environmental insults can aggravate existing lung diseases, impair pulmonary function, and cause lung disease in children. Outdoor air pollution (ozone and particulates), indoor pollution, diesel exhaust, and household fungi are examples. Environmental tobacco smoke dramatically increases childhood pulmonary morbidity. The impact of other tobacco products such as e-cigarettes and marijuana smoke is unclear but being studied. Smoking family members should be counseled to quit smoking and do everything possible to minimize environmental smoke exposure to the people around them. Homes with mold should have remediation, particularly if children with lung disease are in residence. Ozone exposure can be limited by avoiding outdoor activities during the height of daily ozone levels. Recent data show that improvements in air quality reduce lung function impairments in children.

Pet exposure and infestations such as cockroaches or mice may be a significant trigger in children who have asthma and allergies to the pets or pests. Despite the known risk, many families are reluctant to eliminate the risk of exposure to the pet and smoke exposure of any kind. Limiting exposure to outdoor pollutants may be impossible for many families and children.

The conducting airways include the nose, mouth, pharynx, larynx, trachea, bronchi, and terminal bronchioles. These airways direct inspired air to the gas-exchange units of the lung but do not participate in gas exchange. Airflow obstruction in the conducting airways can occur at extrathoracic sites (eg, above the thoracic inlet) or at intrathoracic sites (eg, below the thoracic inlet). Extrathoracic or upper airway obstruction disrupts the inspiratory phase of respiration and is often manifest by stridor or “noisy breathing.” Intrathoracic obstruction disrupts the expiratory phase of respiration and is often manifest by wheezing and prolongation of the expiratory phase. After assessing whether the obstruction is extrathoracic or intrathoracic the next challenge is to determine if the obstruction is fixed or variable. Fixed obstructions disrupt each breath and the abnormal sounds are consistently heard. Fixed obstructions can be intrinsic to the airway or due to airway compression (extrinsic). They are often associated with anatomic abnormalities that may be amenable to surgical correction (Table 19–4).

Variable obstruction leads to abnormal sounds with breathing that are softer or absent with normal quiet breathing and may sound different with every breath. Variable obstructions are often due to dynamic changes in airway caliber that occurs with laryngomalacia, tracheomalacia, or bronchomalacia. The onset and progression of the obstruction can provide important clues as to the etiology and help determine the urgency of evaluation and management. Obstructions due to dynamic airway collapse often improve with age, whereas fixed obstructions typically progress or fail to improve with age. Acute-onset extrathoracic obstruction is often infectious. Clinical indications that the obstruction is severe include high-pitched stridor or wheezing, biphasic stridor, drooling or dysphagia, poor-intensity breath sounds, severe retractions, and poor color or cyanosis.

Helpful diagnostic studies in the evaluation of extrathoracic obstruction include chest and lateral neck radiographs and bronchoscopy. Patients who have symptoms of severe chronic obstruction should have an electrocardiogram and/or ECHO to evaluate for right ventricular hypertrophy and pulmonary hypertension. Patients suspected to have OSA should have a PSG (see section Sleep-Disordered Breathing). Diagnostic studies for intrathoracic obstruction may include chest radiographs, CT, sweat test, PFTs, and bronchoscopy. In older children, PFTs can differentiate fixed from variable airflow obstruction and may identify the site of obstruction. Other diagnostic studies are dictated by the history and physical findings. If asthma is suspected, a trial of bronchodilators and/or anti-inflammatories should be considered. Treatment should be directed at relieving airway obstruction and correcting the underlying condition if possible.

LARYNGOMALACIA

Laryngomalacia is a congenital disorder in which the cartilaginous support for the supraglottic structures is underdeveloped. It is the most common cause of variable extrathoracic airway obstruction and manifests as intermittent stridor in infants, usually within the first 6 weeks of life. Stridor is generally worse in the supine position, with increased activity, with upper respiratory infections, and during feeding. The diagnosis is established by laryngoscopy, which shows inspiratory collapse of an omega-shaped epiglottis (with or without long, redundant arytenoids). Typically the condition is benign and resolves by the time the child is 2 years old, but occasionally signs can be more severe or persist beyond 2 years of age. In mildly affected patients with no stridor at rest and no retractions, treatment is not usually needed. Surgical epiglottoplasty may be recommended in patients with either severe symptoms of airway obstruction such as stridor with each breath, retractions, OSA, and increased work of breathing or more chronic signs such as feeding difficulties or failure to thrive.

OTHER CAUSES OF CONGENITAL EXTRATHORACIC OBSTRUCTION

Other congenital lesions of the larynx such as laryngeal atresia, laryngeal web, laryngocele and cyst of the larynx, subglottic hemangioma, laryngeal cleft, and subglottic stenosis usually present as fixed extrathoracic obstruction and are best evaluated by direct laryngoscopy.

• Laryngeal atresia, also known as complete high airway obstruction syndrome (CHAOS), presents at birth with severe respiratory distress and is often fatal or requires a fetal EXIT procedure (ex utero intrapartum treatment) with immediate tracheostomy.

• Laryngeal web, representing fusion of the anterior portion of the true vocal cords, is associated with hoarseness, aphonia, and stridor at birth and severe cases require immediate intervention.

• Laryngeal cysts and laryngocoeles present with stridor and significant airway obstruction. Laryngeal cysts are superficial and are generally fluid filled. Laryngocoeles communicate with the interior of the larynx and may be either air- or fluid-filled. Both require surgery or laser therapy.

• Subglottic hemangiomas are a rare cause of upper airway obstruction in infants and are associated with cutaneous vascular lesions of the skin in 50%–60% of patients. Although vascular malformations regress spontaneously, airway obstruction requires intervention. Medical management options include propranolol, systemic steroids, or intralesional steroids. Surgical intervention with laser ablation is usually successful. Tracheostomy is rarely required.

• Laryngeal cleft is an uncommon condition resulting from failure of posterior cricoid fusion. Patients present with dysphagia or silent aspiration. A type 1 laryngeal cleft (at the level of the vocal cords) may not show aspiration on a VFSS while more severe types 2 and 3 laryngeal clefts almost always do. All types of clefts may result in recurrent or chronic pneumonia and failure to thrive. The diagnosis is made by rigid laryngoscopy/bronchoscopy with attention to spreading the posterior glottic structures apart and assessing for the absence of tissue above the vocal folds. The decision to correct type 1 clefts should be made after multidisciplinary consideration of the pulmonary complications and other comorbidities. Repair of type 1 clefts may be addressed surgically or with an injection laryngoplasty. More severe clefts require surgical repair and may require tracheostomy. Normal swallow function without aspiration may not return for months, even after repair.

• Subglottic stenosis can be congenital or acquired (see acquired disorders of the extrathoracic airway).

Acquired disorders of the extrathoracic airway can present acutely or with recurrent symptoms of upper airway obstruction. Children with acquired disorders of the extrathoracic airway present with inspiratory sounds consistent with stridor. The pitch of the sound varies depending on the diagnosis. Upper airway obstruction can progress quickly and may be life threatening, requiring close observation. The differential for acquired disorders includes aspiration, infection, and injury or trauma leading to vocal cord paralysis or subglottic stenosis.

FOREIGN-BODY ASPIRATION IN THE EXTRATHORACIC AIRWAY

Aspiration of a foreign body into the respiratory tract is a significant cause of accidental death each year. The foreign body can lodge anywhere along the respiratory tract. Foreign bodies that lodge in the esophagus may compress the airway and cause respiratory distress. More typically, the foreign body lodges in the supraglottic airway, triggering protective reflexes that result in laryngospasm. Small objects such as coins may pass through the glottis and obstruct the trachea. Objects that pass into the lower airway cause coughing and more variable respiratory distress (see section Acquired Causes of Intrathoracic Airway Obstruction).

Foreign-body aspiration is commonly seen with small, round foods such as nuts and seeds, berries, corn/popcorn, hot dogs, and beans. Children 6 months to 3 years are at the highest risk. Homes and child care centers in which an older sibling or child feeds age-inappropriate foods (eg, peanuts, hard candy, or carrot slices) to the younger child are typical in the history. Without treatment, progressive cyanosis, loss of consciousness, seizures, bradycardia, and cardiopulmonary arrest can follow.

Clinical Findings

Signs at the time of aspiration can include coughing, choking, or wheezing. Onset is generally abrupt, with a history of the child running with food in the mouth or playing with seeds, small coins, or toys.

The diagnosis is established by acute onset of choking along with inability to vocalize or cough and cyanosis with marked distress (complete obstruction), or with drooling, stridor, and ability to vocalize (partial obstruction). Chest x-rays and other imaging studies have been used to evaluate for foreign-body ingestion; however, rigid bronchoscopy is the gold standard for diagnosis.

Treatment

Prevention is paramount. Pediatricians should counsel caregivers regarding age-specific safe foods. Small toys and latex balloons should have age-appropriate choking warnings on their labels. In the event of acute upper airway obstruction due to foreign-body aspiration, emergency treatment depends on the amount of obstruction. If partial obstruction is present, the choking subject should be allowed to use his or her own cough reflex to remove the foreign body. If the obstruction increases or the airway is completely obstructed, acute intervention is required and Red Cross recommendations for choking in a child should be followed. https://www.redcross.org/take-a-class/first-aid/performing-first-aid/child-baby-first-aid.

Blind finger sweeps should not be performed in infants or children because the finger may push the foreign body further into the airway. The airway should be opened by jaw thrust, and if the foreign body can be directly visualized, careful removal with the fingers or instruments should be attempted. Patients with persistent apnea and inability to achieve adequate ventilation may require emergency intubation, tracheotomy, or needle cricothyrotomy, depending on the setting and the rescuer’s skills. If the child of any age becomes unresponsive, cardiopulmonary resuscitation (CPR) is recommended. Chest compressions may help to dislodge the foreign body. If the foreign body moves into the lower airway, foreign-body removal is most successfully performed using rigid bronchoscope under general anesthesia.

CROUP SYNDROMES

Croup describes acute inflammatory diseases of the larynx, including viral croup (laryngotracheobronchitis), epiglottitis (supraglottitis), and bacterial tracheitis. These are the main entities in the differential diagnosis for patients presenting with acute stridor, although spasmodic croup, angioedema, laryngeal or esophageal foreign body, and retropharyngeal or peritonsillar abscess should be considered as well.

1. Viral croup

Viral croup generally affects young children 6 months to 5 years of age in the fall and early winter and is most often caused by parainfluenza virus serotypes. However, many other viral organisms as well as M pneumoniae can cause croup. Edema in the subglottic space accounts for the predominant signs of upper airway obstruction although inflammation of the entire airway is often present.

Clinical Findings

A. Symptoms and Signs

Usually, a prodrome of upper respiratory tract symptoms is followed by a barking cough and stridor. Fever is usually absent. Patients with mild disease may have stridor when agitated. As obstruction worsens, stridor occurs at rest, accompanied in severe cases by retractions, air hunger, and cyanosis. On examination, the presence of cough and the absence of drooling favor the diagnosis of viral croup over epiglottitis.

B. Imaging

Anteroposterior and lateral neck radiographs are not routinely indicated for patients with classic presentation of croup. For atypical presentation, x-ray shows subglottic narrowing (the steeple sign) without the irregularities seen in tracheitis and a normal epiglottis. A severely ill patient should never be left unattended in the imaging suite.

Treatment

Treatment of viral croup is based on the symptoms. Mild croup, signified by a barking cough and no stridor at rest, requires supportive therapy with oral hydration and minimal handling. Mist therapy has historically been used, but clinical studies do not demonstrate effectiveness. Conversely, patients with stridor at rest require active intervention. Oxygen should be administered to patients with oxygen desaturation. Nebulized racemic epinephrine (0.5 mL of 2.25% solution diluted in sterile saline) is commonly used because it has a rapid onset of action within 10–30 minutes. Both racemic epinephrine and epinephrine hydrochloride (L-epinephrine, an isomer) are effective in alleviating symptoms and decreasing the need for intubation.

The efficacy of glucocorticoids in croup is firmly established. Dexamethasone, 0.6 mg/kg intramuscularly as one dose, improves symptoms, reduces the duration of hospitalizations and frequency of intubations, and permits earlier discharge from the emergency department. Oral dexamethasone (0.15 mg/kg) may be equally effective for mild to moderate croup. Dexamethasone has been shown to be more effective than prednisolone in equivalent doses, but inhaled budesonide (2–4 mg) can improve symptoms and decrease hospital stay and may be as effective as dexamethasone. The use of heliox, a mixture of helium and oxygen, improves turbulent airflow but is not superior to nebulized medication. Its use is limited in hypoxic children because of its low fractional concentration of inspired oxygen.

If symptoms resolve within 3–4 hours of glucocorticoids and nebulized epinephrine, patients can safely be discharged without fear of a sudden rebound in symptoms. If, however, recurrent nebulized epinephrine treatments are required or if respiratory distress persists, patients require hospitalization for close observation, supportive care, and nebulization treatments as needed. In patients with impending respiratory failure, an airway must be established. Intubation with an endotracheal tube of slightly smaller diameter than would ordinarily be used is reasonably safe. Extubation should be accomplished within 2–3 days to minimize the risk of laryngeal injury. Other underlying causes should be considered in hospitalized patients with persistent symptoms over 3–4 days despite treatment.

Prognosis

Most children with viral croup have an uneventful course and improve within a few days. Some evidence suggests that patients with a history of croup associated with wheezing may have airway hyperreactivity. It is not always clear if the hyperreactivity was present prior to the croup episode or if the viral infection causing croup altered airway function.

2. Epiglottitis

With the introduction of the Haemophilus influenzae conjugate vaccine, the incidence of epiglottitis is rare in countries with immunization programs. If disease occurs, it is likely to be associated with H influenzae in unimmunized children, or another organism such as nontypeable H influenzae, Neisseria meningitidis, or Streptococcus species in immunized populations.

Clinical Findings

A. Symptoms and Signs

The classic presentation is a sudden onset of high fever, dysphagia, drooling, muffled voice, inspiratory retractions, cyanosis, and soft stridor. Patients often sit in the so-called sniffing dog position, with the neck hyperextended and the chin stretched forward, which gives them the best airway possible under the circumstances. Progression to total airway obstruction may occur and result in respiratory arrest. The definitive diagnosis is made by direct inspection of the epiglottis, a procedure that should be done by an experienced airway specialist under controlled conditions (typically in the operating room during intubation). The typical findings are a cherry-red and swollen epiglottis and swollen arytenoids.

B. Imaging

Diagnostically, lateral neck radiographs may be helpful in demonstrating a classic “thumbprint” sign caused by the swollen epiglottis. Obtaining radiographs, however, may delay important airway intervention.

Treatment

Once the diagnosis of epiglottitis is made, endotracheal intubation must be performed immediately in children but not necessarily in adults. Most anesthesiologists prefer general anesthesia (but not muscle relaxants) to facilitate intubation. After an airway is established, cultures of the blood and epiglottis should be obtained, and the patient should be started on appropriate intravenous antibiotics to cover H influenzae and Streptococcus species (ceftriaxone sodium or an equivalent cephalosporin). Extubation can usually be accomplished in 24–48 hours, when direct inspection shows a significant reduction in the size of the epiglottis. Intravenous antibiotics should be continued for 2–3 days, followed by oral antibiotics to complete a 10-day course.

Prognosis

Prompt recognition and appropriate treatment usually results in rapid resolution of swelling and inflammation. Recurrence is unusual.

3. Bacterial Tracheitis

Bacterial tracheitis (pseudomembranous croup) is a severe life-threatening form of laryngotracheobronchitis. As the management of severe viral croup has been improved with the use of dexamethasone, and vaccination has decreased the incidence of epiglottitis, tracheitis is relatively more common as a cause of a pediatric airway emergency requiring admission to the pediatric intensive care unit. This diagnosis must be high in the differential when a patient presents with severe upper airway obstruction and fever. The organism most often isolated is S aureus, but organisms such as H influenzae, group A Streptococcus pyogenes, Neisseria species, Moraxella catarrhalis, and others have been reported. A viral prodrome is common. Viral coinfections are described and influenza should be treated. The disease probably represents localized mucosal invasion of bacteria in patients with primary viral croup, resulting in inflammatory edema, purulent secretions, and pseudomembranes. Although cultures of the tracheal secretions are frequently positive, blood cultures are almost always negative.

Clinical Findings

A. Symptoms and Signs

The early clinical picture is similar to that of viral croup. However, instead of gradual improvement, patients develop higher fever, toxicity, and progressive or intermittent severe upper airway obstruction that is unresponsive to standard croup therapy. The incidence of sudden respiratory arrest or progressive respiratory failure is high, requiring airway intervention. Findings of toxic shock and the acute respiratory distress syndrome may also be seen. Aggressive medical treatment and debridement is indicated.

B. Laboratory Findings and Imaging

The white cell count is usually elevated with a left shift. Cultures of tracheal secretions usually demonstrate one of the causative organisms. Lateral neck radiographs show a normal epiglottis but severe subglottic and tracheal narrowing. Irregularity of the contour of the proximal tracheal mucosa can frequently be seen radiographically and should elicit concern for tracheitis. Bronchoscopy showing a normal epiglottis and the presence of copious purulent tracheal secretions and membranes confirms the diagnosis.

Treatment

Patients with suspected bacterial tracheitis may require direct visualization of the airway in a controlled environment and debridement of the airway. Most patients will be intubated because the incidence of respiratory arrest or progressive respiratory failure is high. Patients may also require further debridement, humidification, frequent suctioning, and intensive care monitoring to prevent endotracheal tube obstruction by purulent tracheal secretions. Intravenous antibiotics to cover S aureus, H influenzae, and the other organisms are indicated. Thick secretions persist for several days, usually resulting in longer periods of intubation for bacterial tracheitis than for epiglottitis or croup. Despite the severity of this illness, the reported mortality rate is very low if it is recognized and treated promptly.

VOCAL FOLD IMMOBILITY

Unilateral or bilateral vocal fold (cord) paresis and paralysis may be congenital, or more commonly may result from injury to the recurrent laryngeal nerves. Patients may present with varying degrees of hoarseness, dysphagia, or high-pitched stridor. If partial function is preserved (paresis), the adductor muscles tend to move better than the abductors, with a resultant high-pitched inspiratory stridor and normal voice. Risk factors for acquired paresis/paralysis include difficult delivery (especially face presentation), neck and thoracic surgery (eg, ductal ligation or repair of tracheoesophageal fistula), trauma, mediastinal masses, and central nervous system disease (eg, Arnold-Chiari malformation). Unilateral cord paralysis is more likely to occur on the left because of the longer course of the left recurrent laryngeal nerve and its proximity to major thoracic structures. With bilateral cord paralysis, the closer to midline the cords are positioned, the greater the airway obstruction; the more lateral the cords are positioned, the greater the tendency to aspirate and experience hoarseness or aphonia.

Airway intervention (tracheostomy) is rarely indicated in unilateral paralysis but is often necessary for bilateral paralysis. Clinically, paralysis can be assessed by direct visualization of vocal fold function with laryngoscopy or more invasively by recording the electrical activity of the muscles (electromyography). Electromyogram recordings can differentiate vocal fold paralysis from arytenoid dislocation, which has prognostic value. Recovery is related to the severity of nerve injury and the potential for healing.

SUBGLOTTIC STENOSIS

Subglottic stenosis may be congenital, or more commonly may result from endotracheal intubation. Neonates and infants are particularly vulnerable to subglottic injury from intubation. The subglottis is the narrowest part of an infant’s airway, and the cricoid cartilage, which supports the subglottis, is the only cartilage that completely encircles the airway. This area is therefore susceptible to injury when an endotracheal tube is inserted. The clinical presentation may vary from asymptomatic to severe upper airway obstruction. Subglottic stenosis should be suspected in children who repeatedly fail extubation or children with multiple, prolonged, or severe episodes of croup. Diagnosis is made by direct visualization of the subglottic space with bronchoscopy and maneuvers to size the airway. Tracheostomy is often required when airway compromise is severe. Laryngotracheal reconstruction, in which a cartilage graft from another source (eg, rib) is used to expand the airway, has become the standard procedure for severe subglottic stenosis in children. In mild cases, balloon dilation of the subglottis is a less invasive alternative.

Congenital disorders of intrathoracic airway obstruction can present acutely or with recurrent symptoms of lower airway obstruction. Children with disorders of the intrathoracic airway often present with expiratory sounds such as wheeze, recurrent cough, and/or recurrent pneumonia due to retained secretions. The differential for intrathoracic airway obstruction includes airway malacia, extrinsic compression (eg, vascular ring), and congenital anomalies such as bronchogenic cysts.

MALACIA OF AIRWAYS

Pathogenesis

Tracheomalacia or bronchomalacia exists when the cartilaginous framework of the airway is inadequate to maintain airway patency. Airway collapse is dynamic and can lead to partial or complete airway obstruction. Because infant airway cartilage is normally soft, infants have some degree of dynamic collapse of the central airway during the phases of respiration. Tracheomalacia and bronchomalacia can be congenital or acquired, although comorbidities associated with congenital tracheomalacia overlap with acquired causes. Congenital or innate abnormalities of the trachealis or tracheal cartilage are associated with developmental syndromes and other congenital abnormalities such as tracheoesophageal fistula and vascular ring. Congenital tracheomalacia may be localized or diffuse and may extend through to the remainder of the conducting airways (bronchomalacia). Acquired tracheomalacia has been associated with long-term ventilation of preterm infants due to delayed cartilaginous development with or without direct positive pressure. Other acquired causes include severe tracheobronchitis, surgical repair of airways anomalies such as tracheoesophageal fistula and complete tracheal rings, extrinsic airway compression due to tumors, abscess or cysts, and compression as seen in congenital heart disease with associated ventricular hypertrophy or vascular anomalies.

Clinical Findings

Coarse and recurrent wheezing, cough, or stridor that do not respond to bronchodilators are common findings. Preterm infants with trachea or bronchomalacia may have hypoxemia that requires continuous nasal cannula or positive pressure ventilation. Symptoms classically present insidiously over the first few months of life and can increase with agitation, excitement, activity, or upper respiratory tract infections. Diagnosis can be made by bronchoscopy or combined inspiratory/expiratory imaging modalities like CT or MRI.

Treatment

Observation is usually indicated for mild symptoms, which generally improve over time with growth. Coexisting lesions such as tracheoesophageal fistulas and vascular rings need primary repair. In severe cases of tracheomalacia, non-invasive or invasive ventilation may be necessary. Unfortunately, tracheostomy alone is seldom satisfactory because airway collapse continues to exist below the tip of the artificial airway. Surgical intervention (posterior tracheopexy, aortopexy, or stents) may be considered for the most challenging situations.

Prognosis

The resolution of symptoms due to airway malacia depends on the severity and extent of the airway malacia and any underlying illness in the child. Children with mild malacia without other underlying lung disease or neuromuscular disease will most likely have at least partial resolution by the time they are 3–4 years old.

VASCULAR RINGS & SLINGS

The most common vascular anomaly to compress the trachea or esophagus is a vascular ring. A vascular ring can be formed by a double aortic arch or a right aortic arch with left ligamentum arteriosum or a patent ductus arteriosus. The pulmonary sling is created when the left pulmonary artery branches off the right pulmonary artery. Other common vascular anomalies include an anomalous innominate artery, a left carotid artery, and an aberrant right subclavian artery. All but the right subclavian artery can cause tracheal compression. The pulmonary sling may compress the trachea but can also compress the right upper lobe bronchus or the right mainstem takeoff. A pulmonary sling is associated with long segment tracheal stenosis 50% of the time.

Clinical Findings

A. Symptoms and Signs

Symptoms of chronic airway obstruction (stridor, coarse wheezing, and croupy cough) are often worse in the supine position. Respiratory compromise is most severe with double aortic arch and may lead to apnea, respiratory arrest, or even death. Esophageal compression may result in feeding difficulties. UGI fluoroscopy series showing esophageal compression is the mainstay of diagnosis in all but anomalous innominate or carotid artery. Chest radiographs and echocardiograms may miss abnormalities. Anatomy can be further defined by angiography, chest CT with contrast, MRI or magnetic resonance angiography, or bronchoscopy.

Treatment

Patients with significant symptoms require surgical correction, especially those with double aortic arch. Patients usually improve following correction but may have persistent but milder symptoms of airway obstruction due to associated tracheomalacia.

BRONCHOGENIC CYSTS

Bronchogenic cysts generally occur in the middle mediastinum (see section Mediastinal Masses) near the carina and adjacent to the major bronchi but can be found elsewhere in the lung. They range in size from 2 to 10 cm. Cyst walls are thin and may contain air, pus, mucus, or blood. Cysts develop from abnormal lung budding of the primitive foregut and can occur in conjunction with other congenital pulmonary malformations such as pulmonary sequestration or lobar emphysema.

Clinical Findings

Bronchogenic cysts can present acutely with respiratory distress in early childhood due to airway compression or with symptoms of infection. Other patients present with chronic symptoms such as chest pain, chronic wheezing, cough, intermittent tachypnea, recurrent pneumonia, or recurrent stridor, depending on the location and size of the cysts and the degree of airway compression. Still other patients remain asymptomatic until adulthood. However, all asymptomatic cysts will eventually become symptomatic; chest pain is the most common presenting complaint. The physical examination is often normal.

A. Laboratory Findings and Imaging Studies

The choice of diagnostic studies for bronchogenic cysts is controversial. Chest radiographs can show air trapping and hyperinflation of the affected lobes or may show a spherical lesion with or without an air-fluid level. However, smaller lesions may not be seen on chest radiographs. CT scan is the preferred imaging study and can differentiate solid versus cystic mediastinal masses and define the cyst’s relationship to the airways and the rest of the lung. Fluoroscopy can help determine whether the lesion communicates with the gastrointestinal tract. MRI and ultrasound are other imaging modalities used.

Treatment

Treatment is surgical resection. Resection should be performed as soon as the cyst is detected to avoid future complications including infection. Postoperatively, vigorous pulmonary physiotherapy is required to prevent complications (atelectasis or infection of the lung distal to the site of resection of the cyst).

Acquired disorders of intrathoracic airway obstruction airway can present acutely or with recurrent symptoms of lower airway obstruction. Children with disorders of the intrathoracic airway often present with expiratory sounds such as wheeze, recurrent cough, and/or recurrent pneumonia due to retained secretions. The differential for intrathoracic airway obstruction includes foreign-body aspiration, infection, extrinsic compression not present at birth (eg, lymphadenopathy), and chronic lung diseases causing airway swelling such as disorders of mucociliary clearance, recurrent aspiration, and asthma.

FOREIGN-BODY ASPIRATION IN THE INTRATHORACIC AIRWAY

Clinical Findings

A. Symptoms and Signs

Respiratory symptoms and signs vary depending on the site of obstruction and the duration following the acute episode. (See section Foreign-Body Aspiration in the Extrathoracic Airway.) The acute cough or wheezing caused by a foreign body in the lower respiratory tract may diminish over time only to recur later as chronic cough or persistent wheezing, monophonic wheezing, asymmetrical breath sounds on chest examination, or recurrent pneumonia in one location. Foreign-body aspiration should be suspected in children with chronic cough, persistent wheezing, or recurrent pneumonia. Asymmetrical breath sounds or localized wheezing also suggests a foreign body.

B. Laboratory Findings and Imaging Studies

Inspiratory and forced expiratory (obtained by manually compressing the abdomen during expiration) chest radiographs should be obtained if foreign-body aspiration is suspected. Chest radiographs may be normal up to 17% of the time. A positive forced expiratory study shows unilateral hyperinflation. There also may be a mediastinal shift away from the affected side. If obstruction of a distal airway is complete, atelectasis and related volume loss will be the major radiologic findings. Virtual bronchoscopy and CT are alternative approaches for detecting a foreign body.

C. Treatment

When a foreign body is highly suspected, a normal chest radiograph is not sufficient to rule out the possibility of an airway foreign body. If clinical suspicion persists based on two of three findings—history of possible aspiration, focal abnormal lung examination, or an abnormal chest radiograph—then a bronchoscopy is indicated. Rigid bronchoscopy under general anesthesia is recommended. Flexible bronchoscopy may be helpful for follow-up evaluations (after the foreign object has been removed).

Children with suspected acute foreign-body aspiration should be admitted to the hospital for evaluation and treatment. Chest postural drainage is no longer recommended because the foreign body may become dislodged and obstruct a major central airway. Bronchoscopy should not be delayed in children with respiratory distress but should be performed as soon as the diagnosis is made—even in children with more chronic symptoms. Following the removal of the foreign body, β-adrenergic nebulization treatments followed by chest physiotherapy are recommended to help clear related mucus or treat bronchospasm. Failure to identify a foreign body in the lower respiratory tract can result in bronchiectasis or lung abscess. This risk justifies an aggressive approach to suspected foreign bodies in suspicious cases.

Mucociliary clearance is the primary defense mechanism for the lung. Inhaled particles including microbial pathogens are also entrapped in mucus on the airway surface, then cleared by the coordinated action of cilia. The volume and composition of airway surface liquid influence the efficiency of ciliary function and mucus clearance. Mucus that cannot be cleared normally can obstruct the airways. If mucociliary clearance is not normal, bacteria that are not cleared can cause a vicious cycle of infection and inflammation and increased mucus production. The two main genetic diseases of mucociliary clearance involve disorders of ion transport (cystic fibrosis [CF]) and disorders in ciliary function (primary ciliary dyskinesia [PCD]).

CYSTIC FIBROSIS

Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disease, results in a syndrome of chronic sinopulmonary infections, malabsorption, and nutritional abnormalities. It is one of the most common lethal genetic diseases in the United States, with an incidence of approximately 1:3000 among Caucasians and 1:9200 in the US Hispanic population. Although abnormalities occur in the hepatic, gastrointestinal, and male reproductive systems, lung disease is the major cause of morbidity and mortality. Most individuals with CF develop obstructive lung disease associated with chronic infection that leads to progressive loss of pulmonary function.

The cause of CF is a defect in a single gene on chromosome 7 that encodes an epithelial chloride channel called the CF transmembrane conductance regulator (CFTR) protein. The most common mutation is F508del, although approximately 1800 other disease-causing mutations been identified. Gene mutations lead to absence or defects in CFTR, altering salt and water movement across cell membranes, resulting in abnormally thick secretions in various organs and critically altering host defense in the lung.

Clinical Findings

A. Symptoms and Signs

All states in the United States and many other countries now perform newborn screening for CF by measuring immunoreactive trypsin (IRT), a pancreatic enzyme, in blood with or without concurrent DNA testing. Most infants with CF have elevated IRT in the newborn period, although false-negative results are possible. In newborns with positive newborn screen, the diagnosis of CF must be confirmed by sweat testing, mutation analysis, or both (http://www.cff.org/AboutCF/Testing/NewbornScreening/).

Approximately 15% of newborns with CF are born with meconium ileus, a severe intestinal obstruction resulting from inspissation of tenacious meconium in the terminal ileum. Meconium ileus is virtually diagnostic of CF, so the infant should be treated presumptively as having CF until a sweat test or genotyping can be obtained.

During infancy and beyond, a common presentation of CF is failure to thrive due to malabsorption from exocrine pancreatic insufficiency, failure of the pancreas to produce sufficient enzymes to digest fats and protein. Children with pancreatic insufficiency fail to gain weight despite good appetite and typically have frequent, bulky, foul-smelling, oily stools. Pancreatic insufficiency occurs in about 85% of persons with CF. (Chapter 22 describes gastrointestinal and hepatobiliary manifestations of CF; see also Table 22–12.) Infants with undiagnosed CF may also present with hypoproteinemia, anemia, and deficiency of the fat-soluble vitamins A, D, E, and K, because of ongoing steatorrhea.

CF should also be considered in children who present with severe dehydration and hypochloremic alkalosis, bronchiectasis, nasal polyps, chronic sinusitis, rectal prolapse, or unexplained pancreatitis or cirrhosis. Respiratory symptoms can include productive cough, wheezing, recurrent pneumonia, progressive obstructive airways disease, exercise intolerance, dyspnea, or hemoptysis. Chronic airway infection with bacteria, including Staphylococcus aureus and H influenzae, often begins in the first few months of life, even in asymptomatic infants. Eventually, Pseudomonas aeruginosa and other gram-negative opportunistic bacteria become the predominant pathogens. Chronic infection leads to airflow obstruction and progressive airway and lung destruction resulting in bronchiectasis.

Episodic increases in respiratory symptoms are generically termed pulmonary exacerbations. Clinically, an exacerbation manifests by increased cough and sputum production, decreased exercise tolerance, malaise, and weight loss, and decrease in measures of lung function. Treatment for pulmonary exacerbations generally consists of antibiotics and augmented airway clearance.

B. Laboratory Findings and Imaging Studies

The diagnosis of CF is made by a sweat chloride concentration greater than 60 mmol/L following an abnormal newborn screen or when obtained for clinical signs or family history of CF. Sweat testing should be performed at a Cystic Fibrosis Foundation–accredited laboratory. A diagnosis can also be confirmed by genotyping that reveals two disease-causing CFTR mutations (www.cftr2.org).

Intermediate sweat chloride values of 30–60 may be associated with “mild” CFTR mutations that result in residual functioning CFTR protein. Patients with residual CFTR function typically have adequate pancreatic exocrine function, but may develop severe lung disease. CFTR-related metabolic syndrome, diagnosed based on elevated IRT on newborn screen but sweat test less than 60 mmol/L and up to two CFTR mutations, at least one of which is not considered disease-causing, appears to have an even milder disease phenotype. The natural history of this condition is still being defined.

Treatment

Individuals with CF should be followed at a Cystic Fibrosis Foundation–accredited CF care center (http://www.cff.org) in addition to a primary care provider. Care is provided by a multidisciplinary team that includes pulmonologists and advanced practice providers trained in CF care, nurses, respiratory therapists, dietitians, social workers, and psychologists. Recently a large study highlighted the importance of screening for depression and anxiety in patients with CF, as these are prevalent and negatively impact quality of life and adherence to treatment.

The cornerstone of gastrointestinal treatment is pancreatic enzyme supplementation combined with a high-calorie, high-protein, and high-fat diet. Persons with CF are required to take pancreatic enzyme immediately prior to each meal and with snacks and should also take daily multivitamins that contain vitamins A, D, E, and K. Caloric supplements are often added to the diet to optimize growth. Daily salt supplementation also is required to prevent hyponatremia, especially during hot weather.

Airway clearance therapy and aggressive antibiotic use form the mainstays of treatment for CF lung disease. Antibiotic therapy appears to be one of the primary reasons for the increased life expectancy of persons with CF. Respiratory treatments typically include recombinant human dornase alpha, inhaled hypertonic saline, and for those with chronic Pseudomonas infection, anti-pseudomonal antibiotics (tobramycin or aztreonam), and oral azithromycin. These therapies have been shown to maintain lung function and reduce the need for hospitalizations and intravenous antibiotics. Early detection of P aeruginosa and treatment with inhaled tobramycin can often eradicate the bacteria and delay chronic infection. Bronchodilators and anti-inflammatory therapies are also frequently used.

Recent development of protein-rescue therapies that directly target the underlying defects in CFTR (termed CFTR modulators) have made significant impacts on the lives of patients with CF. The first treatment that directly works to correct the function of the defective CF protein was approved in 2012, and currently there are three CFTR modulators that are FDA approved for people with certain CFTR mutations: ivacaftor, lumacaftor/ivacaftor, and tezacaftor/ivacaftor. These medications are currently available to about 50% of the CF population based on genotype. Addition of these modulators to treatment regimens significantly improves lung function and body mass index and reduces exacerbations. Recently, there have been promising results from clinical trials of “triple” combination CFTR modulators that would extend CFTR modulator access to approximately 90% of the CF population.

Prognosis

A few decades ago, CF was fatal in early childhood. Now the median life expectancy is 70 years of age. The rate of lung disease progression usually determines survival. Lung transplantation may be performed in those with end-stage lung disease. In addition, new treatments, including gene therapy and gene editing trials and improved CFTR modulators, are in development to improve life expectancy and quality of life.

PRIMARY CILIARY DYSKINESIA

PCD is a rare, genetic disorder (usually inherited in an autosomal recessive fashion) of impaired mucociliary clearance leading to chronic otosinopulmonary disease. It is believed to occur in approximately 1 in 15,000 births. Approximately half of patients with PCD have situs abnormalities, and men are usually infertile. The triad of situs inversus totalis, bronchiectasis, and chronic sinusitis is known as Kartagener syndrome.

Clinical Findings

A. Symptoms and Signs

Upper and lower respiratory tract manifestations are cardinal features of PCD. The majority of children with PCD present in the immediate newborn period with respiratory distress (commonly diagnosed as neonatal pneumonia or transient tachypnea of the newborn) and often require supplemental oxygen. Upper respiratory tract problems include chronic year-round nasal drainage that may begin in the first weeks of life, chronic sinusitis, nasal polyps, and chronic serous otitis media. Conductive hearing loss with chronic middle ear effusion is common. If myringotomy tubes are placed, chronic otorrhea often ensues. Lower respiratory tract features include chronic year-round productive cough, chronic and recurrent bronchitis, and recurrent pneumonia. They are at risk to develop obstructive lung disease and bronchiectasis. Situs inversus totalis occurs in approximately 50% of patients with PCD.

Nonrespiratory ciliopathies that have been associated with PCD include heterotaxy, with congenital heart disease, asplenia, polysplenia, autosomal dominant polycystic kidney disease, retinitis pigmentosa, and biliary atresia.

B. Laboratory Findings and Imaging Studies

The diagnosis of PCD currently requires a compatible clinical phenotype with at least two of four key clinical features: (1) unexplained neonatal respiratory distress in term infant, (2) year-round daily cough, (3) year-round daily nasal congestion, and (4) organ laterality defect. Additionally, identification of low nasal nitric oxide, biallelic pathogenic mutations in PCD-associated genes, and/or ultrastructural defects of the cilia by EM is also required. In patients with a compatible clinical history, nasal nitric oxide at a PCD specialty center is the preferable diagnostic test in cooperative children ages 5 and older. Extended genetic testing (> 12 genes) has emerged as the test of choice if nasal nitric oxide testing is not available. Cilia samples may be obtained from either the upper airways (nasal passage) or lower airways (trachea) for EM testing. Significant expertise is required to produce high-quality EM of cilia, and to distinguish primary (genetic) defects from secondary (acquired) defects in ciliary ultrastructure. Multiple different defects in EM include abnormalities in the outer dynein arms, inner dynein arms, radial spokes, and the central apparatus. Some patients with PCD can also have normal EM ultrastructure. Ciliary beat frequency and motion analysis analyzed via high speed videomicroscopy are also used for diagnosis in some settings.

Treatment

At present, no specific therapies are available to correct the ciliary dysfunction in PCD. Treatment is not evidence-based and recommendations are largely extrapolated from CF and other suppurative lung diseases. Respiratory management includes routine pulmonary monitoring (lung function testing, respiratory cultures, chest imaging), airway clearance by combinations of physiotherapy and physical exercise, and aggressive treatment of upper and lower airways infections.

Prognosis

The progression of lung disease in PCD is quite variable. Importantly, persons with PCD are at risk for chronic obstructive lung disease with bronchiectasis. With monitoring and aggressive treatment during times of illness, most individuals with PCD should experience a normal or near-normal life span.

BRONCHIECTASIS

Pathogenesis

Bronchiectasis is the permanent dilation of bronchi resulting from airway obstruction by retained mucus secretions or inflammation in response to chronic or repeated infection. It occurs either as a consequence of a preceding illness (severe pneumonia or foreign-body aspiration) or as a manifestation of an underlying systemic disorder leading to chronic airway inflammation and injury (CF, PCD, chronic aspiration, or immunodeficiency).

Clinical Findings

A. Symptoms and Signs

Persons with bronchiectasis will typically have chronic cough, purulent sputum, fever, and weight loss. Recurrent respiratory infections and dyspnea on exertion are also common. Hemoptysis occurs less frequently in children than in adults with bronchiectasis. On physical examination, digital clubbing may be seen. Rales, rhonchi, and decreased air entry are often noted over the bronchiectatic areas.

B. Laboratory Findings and Imaging Studies

The most common bacteria detected in cultures from the lower respiratory tract include Streptococcus pneumoniae, Staphylococcus aureus, nontypeable H influenzae, and Pseudomonas aeruginosa. Nontuberculous mycobacterial species may also be detected in patients with bronchiectasis.

Chest radiographs may be mildly abnormal with slightly increased bronchovascular markings or areas of atelectasis, or they may demonstrate cystic changes in one or more areas of the lung. The extent of bronchiectasis is best defined by volumetric chest CT, which often reveals far wider involvement of lung than expected from the chest radiograph. Airflow obstruction and air trapping often is seen on pulmonary function testing. Evaluation of lung function after use of a bronchodilator is helpful in assessing the benefit from bronchodilators. Serial assessments of lung function help define the progression or resolution of the disease.

Differential Diagnosis

Bronchiectasis is the hallmark finding in patients with disorders of mucociliary; thus, CF and PCD must be considered in all children with bronchiectasis. Bronchiectasis has numerous other causes to consider. It can occur following severe respiratory tract infections by bacteria (eg, Bordetella pertussis), viruses (eg, adenovirus), or other atypical organisms (eg, mycobacteria). Bronchiectasis can also be due to persistent inflammation and is commonly seen in persons with recurrent aspiration pneumonia, CF, PCD, immunodeficiency, surfactant deficiencies, and collagen-vascular conditions. Other diagnostic considerations include foreign-body aspiration and allergic bronchopulmonary aspergillosis.

Treatment

Aggressive antibiotic therapy during pulmonary exacerbations and routine airway clearance are mainstays of treatment. Chronic antibiotic use, anti-inflammatory therapy, hyperosmolar agents (hypertonic saline), and bronchodilators have not proven effective in non-CF bronchiectasis, although individual patients may benefit. However, a large study in adults with idiopathic bronchiectasis concluded that those who received dornase alpha twice a day had more frequent exacerbations, hospitalizations, and lower lung function compared to placebo; thus, dornase alpha is not indicated in adult idiopathic bronchiectasis. Chronic azithromycin was recently shown to reduce exacerbations in adults with non-CF bronchiectasis. Whether these results translate to children with idiopathic bronchiectasis is not known.

Surgical removal of an area of lung affected with severe bronchiectasis is considered when the response to medical therapy is poor. Other indications for operation include severe localized disease, repeated hemoptysis, and recurrent pneumonia in one area. If bronchiectasis is widespread, surgical resection offers little advantage.

Prognosis

The prognosis depends on the underlying cause and severity of bronchiectasis, the extent of lung involvement, and the response to medical management. Good pulmonary hygiene and avoidance of infectious complications in the involved areas of lung may reverse cylindrical bronchiectasis.

PULMONARY AGENESIS & HYPOPLASIA

In unilateral pulmonary agenesis (complete absence of one lung), the trachea continues into a main bronchus and often has complete tracheal rings. With compensatory postnatal growth, the remaining lung often herniates into the contralateral chest. Chest radiographs show a mediastinal shift toward the affected side. Absent or incomplete lung development may be associated with vertebral and other congenital abnormalities, such as absence of one or both kidneys or fusion of ribs, and the outcome is primarily related to the severity of associated lesions. About 37% of patients with pulmonary agenesis survive; the mortality rate is higher with agenesis of the right lung than of the left lung.

Pulmonary hypoplasia is incomplete development of one or both lungs, characterized by a reduction in alveolar number and a reduction in airway branches and surface area for gas exchange. Pulmonary hypoplasia results from premature disruption of lung development. Causes include decreased amniotic fluid production (such as with renal agenesis), premature loss of amniotic fluid through prolonged premature rupture of membranes, decreased blood flow to the early fetal developing lungs, chromosomal abnormalities, or possibly a primary mesodermal defect affecting multiple organ systems leading to structural immaturity. Chest cage abnormalities, intrathoracic masses, diaphragmatic hernia or elevation, fetal hydrops, severe musculoskeletal disorders, and cardiac lesions may also result in hypoplastic lungs. Postnatal factors may play important roles. For example, infants with advanced BPD can have pulmonary hypoplasia.

Clinical Findings

A. Symptoms and Signs

The clinical presentation is highly variable and related to the severity of hypoplasia as well as associated abnormalities. Lung hypoplasia is often associated with pneumothorax in newborns. Some newborns present with perinatal stress, severe acute respiratory distress, and persistent pulmonary hypertension secondary to primary pulmonary hypoplasia (without associated anomalies). Children with lesser degrees of hypoplasia may present with chronic cough, tachypnea, wheezing, and recurrent pneumonia.

B. Laboratory Findings and Imaging Studies

Chest radiographic findings include variable degrees of volume loss in a small hemithorax with mediastinal shift. Pulmonary agenesis should be suspected if tracheal deviation is evident on the chest radiograph. The chest CT scan is the optimal diagnostic procedure if the chest radiograph is not definitive, though ultrasound or fetal MRI are also used for prenatal diagnosis. Ventilation-perfusion scans, angiography, and bronchoscopy are often helpful in the evaluation, demonstrating decreased pulmonary vascularity or premature blunting of airways associated with the maldeveloped lung tissue. The degree of respiratory impairment is defined by analysis of arterial blood gases.

Treatment & Prognosis

Treatment is supportive. The outcome is determined by the severity of underlying medical problems, the extent of the hypoplasia, and the degree of pulmonary hypertension.

PULMONARY SEQUESTRATION

Pulmonary sequestration is the second most common congenital lung abnormality, is characterized by nonfunctional pulmonary tissue that does not communicate with the tracheobronchial tree, and receives its blood supply from one or more anomalous systemic arteries. This abnormality originates during the embryonic period of lung development. It is classified as either extralobar or intralobar.

Extralobar sequestration is a mass of pulmonary parenchyma anatomically separate from the normal lung, with a distinct pleural investment. Its blood supply derives from the systemic circulation (more typical), from pulmonary vessels, or from both. In contrast to intralobar sequestrations, venous drainage is usually through the systemic or portal venous system. Pathologically, extralobar sequestration appears as a solitary thoracic lesion near the diaphragm. Abdominal sites are rare. Size varies from 0.5 to 12 cm. The left side is involved in more than 65% of cases. Other congenital anomalies are seen in 50% of patients with extralobar sequestration.

Intralobar sequestration is an isolated segment of lung within the normal pleural investment that often receives blood from one or more arteries arising from the aorta or its branches. Intralobar sequestration is usually found within the lower lobes (98%), 55% are found on the left side, and it is rarely associated with other congenital anomalies (< 2%).

Clinical Findings, Imaging, & Treatment

Pulmonary sequestrations have been detected by prenatal ultrasound. Doppler imaging may allow for distinction between intralobar and extralobar malformations. Postnatal clinical presentation includes chronic cough, wheezing, and/or recurrent pneumonias. Rarely, patients with sequestration present with hemoptysis. Diagnosis is often suggested by CT imaging postnatally, though it can be diagnosed via prenatal ultrasound. CT angiography or magnetic resonance angiography have proved useful in identifying anomalous systemic arterial supply to the lung. Treatment is surgical resection.

CONGENITAL LOBAR OVERINFLATION

Patients with congenital lobar overinflation (CLO)—also known as congenital lobar emphysema—present most commonly with neonatal respiratory distress or progressive respiratory impairment during the first year of life. Rarely the mild or intermittent nature of the symptoms in older children or young adults results in delayed diagnosis. Most patients are white males. Although the cause of congenital lobar emphysema is not well understood, some lesions show bronchial cartilaginous dysplasia due to abnormal orientation or distribution of the bronchial cartilage or other cause of bronchial obstruction, leading to a partial ball-valve effect and resultant air trapping. This leads to expiratory collapse, producing obstruction, and air trapping.

Clinical Findings

A. Symptoms and Signs

Clinical features include respiratory distress, tachypnea, wheezing, and cough. Breath sounds are reduced on the affected side, perhaps with hyperresonance to percussion, mediastinal displacement, and bulging of the chest wall.

B. Imaging Studies

Radiologic findings include overdistention of the affected lobe (usually an upper or middle lobe; > 99%), with wide separation of bronchovascular markings, collapse of adjacent lung, shift of the mediastinum away from the affected side, and a depressed diaphragm on the affected side. The radiographic diagnosis may be confusing in the newborn because of retention of alveolar fluid in the affected lobe causing the appearance of a homogeneous density. The most commonly used diagnostic studies are chest CT and bronchoscopy.

Differential Diagnosis

The differential diagnosis of CLO includes pneumothorax, pneumatocele, atelectasis with compensatory hyperinflation, diaphragmatic hernia, and congenital cystic adenomatoid malformation. The most common site of involvement is the left upper lobe (42%) or right middle lobe (35%). Evaluation must differentiate regional obstructive emphysema from lobar hyperinflation secondary to an uncomplicated ball-valve mechanism due to extrinsic compression (ie, bronchogenic cyst, tumor, lymphadenopathy, vascular compression) or intrinsic obstruction from a mucus plug due to infection and inflammation from various causes.

Treatment

When respiratory distress is marked, a segmental or complete lobectomy is usually required. Less symptomatic and older children may do equally well with or without lobectomy.

CONGENITAL PULMONARY AIRWAY MALFORMATION (PREVIOUSLY NAMED CYSTIC ADENOMATOID MALFORMATION)

Congenital pulmonary airway malformations (CPAMs; previously known as congenital cystic adenomatoid malformations) are unilateral hamartomatous lesions that generally present with marked respiratory distress within the first days of life. This disorder accounts for 95% of cases of congenital cystic lung disease.

Right and left lungs are involved with equal frequency. These lesions originate in the first 5–22 weeks of gestation during the embryonic period of lung development. They are space-occupying masses that can appear to be solid or cystic. Histopathology varies based on type of CPAM and may show an increase in terminal respiratory structures, forming intercommunicating cysts of various sizes, lined by cuboidal or ciliated pseudostratified columnar epithelium. Air passages appear malformed and tend to lack cartilage.

There are five types of such malformations (Table 19–5).

Clinical Findings

A. Symptoms and Signs

CPAMs are most commonly identified on routine prenatal ultrasound. In children, 86% are identified by age five. Presenting symptoms include respiratory distress with focal findings of decreased breath sounds, and recurrent pulmonary infection. With type 3 lesions, dullness to percussion may be present. Older patients can present with a spontaneous pneumothorax or with pneumonia-like symptoms.

B. Laboratory Findings and Imaging Studies

Chest radiographic findings differ by the type of lesion. Placement of a radiopaque feeding tube into the stomach helps in the differentiation from diaphragmatic hernia. Differentiation from sequestration is not difficult because congenital CPAMs have no systemic blood supply.

Treatment

Postnatal treatment of types 1 and 3 lesions involves surgical removal of the affected lobe. Attention must be paid to complications of these lesions such as hydrops and cardiac compression. Resection is often indicated because of the risk of infection and air trapping, since the malformation communicates with the tracheobronchial tree but mucus clearance is compromised. Segmental resection is not feasible because smaller cysts may expand after removal of the more obviously affected area. Of note, some CPAMs have been shown to spontaneously resolve. However, CPAMs have been reported to have malignant potential; therefore, expectant management with observation alone should proceed with caution. Recent development of intrauterine surgery for congenital malformations has led to promising results.

BRONCHOPULMONARY DYSPLASIA

BPD remains one of the most significant sequelae of acute respiratory distress in the neonatal intensive care unit, with an incidence as high as 68% for infants born at 22–28 weeks’ gestation. This disease was first characterized in 1967 when Northway reported the clinical, radiologic, and pathologic findings in a group of preterm newborns who required prolonged mechanical ventilation and oxygen therapy.

The pathologic findings and clinical course of BPD have changed over time due to technological advances (artificial surfactant, antenatal steroids) and protective/noninvasive ventilatory strategies. Improvements in care have also increased survival of infants born at earlier gestational ages. Extremely preterm infants born at less than 28 weeks’ gestation are at risk to develop “new” BPD and arrest of lung development, which is characterized by alveolar simplification and vascular hypoplasia that can lead to sequelae, such as impaired gas exchange, exercise intolerance, and pulmonary hypertension.

The mechanisms that cause BPD are unclear. Current studies suggest that structural immaturity of the alveolar-capillary network, surfactant deficiency, atelectasis, and pulmonary edema cause impaired gas exchange and, potentially, respiratory failure. Mechanical ventilation and supplemental oxygen, though necessary to sustain life, may result in barotrauma and oxidative stress. Excessive fluid administration, patent ductus arteriosus, pulmonary interstitial emphysema, pneumothorax, infection, pulmonary hypertension, and inflammatory stimuli secondary to lung injury or infection also play important roles in the pathogenesis of the disease. Infants can develop aggressive, fibroproliferative pathologic lesions as well as physiologic abnormalities (increased airway resistance) and biochemical markers of lung injury that may predict BPD during the first weeks of life. Ongoing injuries may further contribute to ventilator and oxygen dependence. The lungs of extremely preterm newborns with BPD show simplified histology with fewer alveoli, early inflammation, and hypercellularity followed by healing with fibrosis.

Clinical Findings

The clinical definition of BPD includes the need for postnatal oxygen for at least 28 days. The severity of BPD is determined by a physiologic assessment of oxygen status at 36 weeks’ gestation or on day of life for infants born after 32 weeks’ gestation. Full-term newborns with disorders such as meconium aspiration, congenital diaphragmatic hernia, and persistent pulmonary hypertension also can develop BPD.

The clinical course of infants with BPD ranges from an oxygen requirement that gradually resolves over a few months to more severe disease requiring tracheostomy for chronic mechanical ventilation during early childhood. In general, patients show slow, steady improvements in oxygen or ventilator requirements. Sufficient respiratory support should be provided to ensure that the preterm infant breathes comfortably without distress. Clinical management also includes paying careful attention to growth and nutrition (infants with oxygen dependence have high caloric requirements) and partnering with developmental therapists to ensure the optimal neurocognitive outcomes.

Treatment

A. Medical Therapy

Early use of surfactant therapy with adequate lung recruitment increases the chance for survival without BPD, reduces the need for mechanical ventilation, and can decrease mortality. Short courses of postnatal glucocorticoid therapy have been helpful in increasing the success of weaning from the ventilator. Longer courses of postnatal glucocorticoids have been linked to an increased incidence of cerebral palsy. Routine use of inhaled corticosteroids and β-adrenergic agonists do not decrease the incidence of BOD, but there may be some benefit to infants who have airway hyper-reactivity.

Salt and water retention secondary to chronic hypoxemia, hypercapnia, or other stimuli may be present. Chronic or intermittent diuretic therapy is commonly used if pulmonary edema is present. Clinical studies show acute improvement in lung function with this therapy, but their impact on long-term outcomes is unclear. Unfortunately, diuretics often have adverse effects, including volume contraction, hypokalemia, alkalosis, hyponatremia, and nephrocalcinosis. Potassium and arginine chloride supplements may be required.

B. Airway Evaluation

Children with significant stridor, sleep apnea, chronic wheezing, or excessive respiratory distress require diagnostic bronchoscopy to evaluate for structural lesions (eg, subglottic stenosis, vocal cord paralysis, tracheal or bronchial stenosis, tracheobronchomalacia, or airway granulomas). The contribution of gastroesophageal reflux and aspiration should be considered in the face of worsening chronic lung disease.

C. Management of Pulmonary Hypertension

Infants with BPD are at risk of developing pulmonary hypertension. In many of these children even mild hypoxemia can cause significant elevations of pulmonary arterial pressure. To minimize the harmful effects of hypoxemia, the arterial oxygen saturation should be kept above 93% in children with pulmonary hypertension, with care to avoid hyperoxia during retinal vascular development. Echocardiograms should be performed to monitor for the development of right ventricular hypertrophy. Management of neonatal pulmonary hypertension should involve expert consultation with a pulmonary hypertension specialist. Cardiac catheterization may be necessary to diagnose unsuspected cardiac or pulmonary lesions and to measure the response of the pulmonary vasculature to vasodilators such as inhaled nitric oxide before chronic therapy, such as oral sildenafil, is initiated. A barium esophagram, esophageal pH/impedence studies, video fluoroscopic swallow study, PSG or overnight pulse oximetry, and bronchoscopy may aid in diagnosing gastroesophageal reflux, aspiration, OSA, and airway abnormalities that contribute to the underlying pathophysiology. Long-term care should include monitoring for systemic hypertension and the development of left ventricular hypertrophy.

D. Nutrition and Immunizations

Nutritional problems in infants with BPD may be due to increased oxygen consumption, feeding difficulties, gastroesophageal reflux, and chronic hypoxemia. Hypercaloric formulas and gastrostomy tubes are often required to ensure adequate intake while avoiding overhydration. Routine vaccinations including the influenza vaccine are recommended. Immune prophylaxis of RSV reduces the severity morbidity of bronchiolitis in infants with BPD. In children older than 2 years with severe BPD, pneumococcal polysaccharide 23-valent vaccine should be considered in addition to standard pneumococcal vaccination.

E. Ventilation

For children with established severe BPD and persistent positive pressure dependence, a supportive approach to ventilation is warranted. The lungs of infants with severe BPD demonstrate very heterogeneous disease with regions of both atelectasis and extreme hyperinflation. In this context, an effective ventilation strategy involves delivery of larger tidal volumes (10–12 mL/kg) given more slowly (inspiratory time ≥ 0.6 seconds) with slower rates (10–14 breaths/min) to permit adequate exhalation. Sufficient peak end-expiratory pressure (PEEP) should be provided to overcome dynamic collapse of the airways. Counterintuitively, increasing PEEP may effectively decrease hyperinflation in infants with severe tracheobronchomalacia. This approach to ventilation can reduce air hunger, prevent hypoxemic spells, and decrease the infant’s work of breathing.

Differential Diagnosis

The differential diagnosis of BPD includes meconium aspiration syndrome, congenital infection (eg, with cytomegalovirus or Ureaplasma), cystic adenomatoid malformation, recurrent aspiration, pulmonary lymphangiectasia, total anomalous pulmonary venous return, overhydration, childhood ILD, and idiopathic pulmonary fibrosis.

Prognosis

Surfactant replacement therapy has had a markedly beneficial effect on reducing morbidity and mortality from BPD. The incidence of BPD and chronic lung disease due to prematurity is increasing due to increased survival or early and extremely preterm infants. The long-term outlook for most survivors is favorable, although follow-up studies suggest that lung function may be altered for life. As smaller, more immature infants survive, abnormal neurodevelopmental outcomes become more likely. The incidence of cerebral palsy, hearing/visual impairment, and developmental delays is increased. Feeding abnormalities, behavior difficulties, and increased irritability have also been reported. A focus on alleviating respiratory distress, optimal nutrition, prophylaxis against respiratory infection, developmental therapies (physical, occupational, and speech), attention to neurocognitive function, and family support provide the best outcomes.

COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA

Community-acquired pneumonia (CAP) is the most common cause of childhood mortality worldwide. Infectious etiologies vary widely by geographic region and by the age of the child. In developed countries the majority of pneumonias are caused by viral infections. Physical examination, white blood cell count and differential, and chest radiograph do not reliably distinguish between viral and bacterial pathogens. Children with CAP complicated by parapneumonic effusions are more likely to have a prolonged illness and are at higher risk for long term complications of CAP. Empyema is covered in the next section of this chapter.

The most common cause of bacterial pneumonia in children of all ages is S pneumoniae, but the spectrum of potential pathogens to be considered also includes aerobic, anaerobic, and acid-fast bacteria as well as other atypical bacteria and respiratory viruses. Bacterial pneumonia usually follows a viral lower respiratory tract infection. Compromised pulmonary defense systems increase the risk of pneumonia in children. For example, abnormal mucociliary clearance, impaired cough function, immunocompromised status, aspiration of oral secretions or oral intake, and malnutrition, increase the risk for bacterial pneumonia. Certain immunocompromised patients, such as those who have undergone splenectomy or who have hemoglobin SS or SC disease or thalassemia, are especially prone to overwhelming sepsis associated with bacterial pneumonia.

Clinical Findings

A. Symptoms and Signs

The pathogen, severity of the infection, and age of the patient may cause substantial variations in the presentation of CAP. Fever (> 39°C), tachypnea, and cough are hallmarks of CAP. Respiratory distress and hypoxemia are signs of more severe disease. Chest auscultation may reveal focal crackles or decreased breath sounds in the setting of consolidation or an associated pleural effusion. Some patients may have additional extrapulmonary findings, such as abdominal pain, due to pneumonia itself. Others may have evidence of infection at other sites due to the same organism causing their pneumonia such as otitis media, sinusitis, or meningitis.

B. Laboratory Findings and Imaging Studies

Chest x-rays may be helpful diagnostic tool in CAP but are not specific to bacterial pneumonia. Chest radiographs are indicated in children ill enough to be in the hospital for CAP to evaluate for complicated CAP. Laboratory studies may also impact the management of children hospitalized for CAP, but they are not indicated for the outpatient management of children with CAP. Blood cultures should be obtained in children admitted to the hospital with severe distress or complicated pneumonia. Inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein (CRP), and procalcitonin may inform clinical decision making, especially in complicated CAP. Complete blood counts can help evaluate for complications of pneumonia such as thrombocytopenia, anemia, or hemolytic uremic syndrome. Sputum cultures may be helpful in older children capable of providing a satisfactory sample. Invasive diagnostic procedures should be undertaken in critically ill patients when other means do not adequately identify the cause (see section Diagnosis of Respiratory Tract Infections).

If a pleural effusion is suspected, radiographs should be taken in the lateral decubitus position. Chest ultrasonography may also be useful to confirm the clinical suspicion and to localize the effusion. A diagnostic (and possibly therapeutic) thoracentesis should also be performed in a child with a pleural effusion. For further recommendations, see section Parapneumonic Effusions & Empyema.

Differential Diagnosis

Noninfectious pulmonary disease (including gastric aspiration, foreign-body aspiration, atelectasis, congenital malformations, congestive heart failure, tumors such as plasma cell granulomas, chronic ILD, and pulmonary hemosiderosis) should be considered in the differential diagnosis of localized or diffuse infiltrates. When effusions are present, additional noninfectious disorders such as collagen vascular diseases, neoplasm, and pulmonary infarction should also be considered.

Treatment

If a bacterial pneumonia is suspected, empiric antibiotic therapy should be considered. Children younger than 4 weeks should be treated with ampicillin and an aminoglycoside. Infants 4–12 weeks of age should be admitted to the hospital and treated with intravenous ampicillin for 7–10 days. Admission to the hospital should also be considered in any child from 3 to 6 months of age with bacterial pneumonia. All children older than 6 months who do not have significant respiratory distress should be treated with oral amoxicillin (50–90 mg/kg/dose) in doses given three times per day for 7–10 days. Macrolide antibiotics should be used if an atypical infection such as M pneumoniae is suspected, although the utility of treating Mycoplasma infections is questionable. (See Chapter 39). When possible, therapy can be guided by the antibiotic sensitivity pattern of the organisms isolated. (For further discussion, see Chapter 39.) Whether older children should be hospitalized depends on age, the severity of illness, the suspected organism, and the anticipated reliability of adherence to the treatment regimen at home. Moderate to severe respiratory distress, apnea, hypoxemia, poor feeding, clinical deterioration on oral antibiotic treatment, or associated complications (large effusions, empyema, or abscess) indicate the need for immediate hospitalization. Careful outpatient follow-up within 12 hours to 5 days is indicated in those not admitted.

Additional therapeutic considerations include oxygen, humidification of inspired gases, hydration and electrolyte supplementation, and nutrition. Removal of pleural fluid for diagnostic purposes is indicated to guide antimicrobial therapy and may be required for therapeutic purposes.

Prognosis

Immunocompetent children who live in developed countries in whom bacterial pneumonia is adequately recognized and treated have a high survival rate. For example, the mortality rate from uncomplicated pneumococcal pneumonia is less than 1%. If the patient survives the initial illness, persistently abnormal pulmonary function following even complicated CAP is surprisingly uncommon, even when treatment has been delayed or inappropriate.

PARAPNEUMONIC EFFUSION & EMPYEMA

Parapneumonic effusions can be associated with pneumonia, autoimmune disease, trauma, malignancy, hypoalbuminemia due to liver or kidney disease, hypothyroidism, autoimmune disease, and pancreatitis. Some parapneumonic effusions associated with pneumonia harbor infection. Others are inflammatory reactions to the infection. The nomenclature in this area is somewhat confusing. Some authors use the term empyema for grossly purulent fluid and parapneumonic effusion for nonpurulent fluid. It is clear, however, that some nonpurulent effusions will also contain organisms and represent either partially treated or early empyema. It is probably best to refer to all effusions associated with pneumonia as parapneumonic effusions, some of which are infected and some not.

The most common organism associated with empyema is S pneumoniae. Other common organisms include H influenzae, and S aureus. Less common causes are group A Streptococcus, gram-negative organisms, anaerobic organisms, and M pneumoniae. Effusions associated with tuberculosis are almost always sterile and constitute an inflammatory reaction.

Clinical Findings

A. Symptoms and Signs

Patients usually present with typical signs of pneumonia, including fever, tachypnea, and cough. Patients with complicated pneumonia may have chest pain, decreased breath sounds, and dullness to percussion on the affected side and may prefer to lie on the affected side. With large effusions, there may be tracheal deviation to the contralateral side. Empyema is more likely to occur in children younger than 5 years and in immunocompromised hosts.

B. Diagnostic Studies

The presence of pleural fluid is suggested by a homogeneous density that obscures the underlying lung on chest radiograph. Large effusions may cause a shift of the mediastinum to the contralateral side. Small effusions may only blunt the costophrenic angle. Lateral decubitus radiographs may help to detect freely movable fluid by demonstrating a layering-out effect, unless the fluid is loculated. Chest ultrasound is preferred to chest CT for identifying septations or loculations. Chest CT scan can help determine the presence of a parenchymal abscess in cases of pneumonia that does not respond as expected.

Blood cultures may be positive up to 18% of the time in complicated pneumonia. The tuberculin skin test is positive in most cases of tuberculosis. Gram stain, cultures, and antigen detection sent from a diagnostic or therapeutic thoracocentesis may help establish the etiology of the pneumonia. Cells in the pleural fluid are usually neutrophils in bacterial disease and lymphocytes in tuberculous effusions. Although in adults the presence of low pH and glucose indicates the need for aggressive and thorough drainage procedures, the prognostic significance of these findings in children is unknown. When the sitology of the effusion is unknown, Light’s criteria should be used to determine if the fluid obtained by thoracocentesis is an exudate or a transudate. Light’s criteria indicate an exudate if one of the following is positive: pleural fluid protein/Serum protein greater than 0.5, pleural fluid lactate dehydrogenase (LDH)/serum LDH greater than 0.6, or pleural fluid LDH greater than 2/3 serum upper limit of normal (mdcalc.com.).

Treatment

After initial thoracentesis and identification of the organism, appropriate intravenous antibiotics and adequate drainage of the fluid are the mainstay of therapy. Although there is a trend toward managing smaller pneumococcal empyemas without a chest tube, larger effusions require chest tube drainage. Early use of fibrinolytics is becoming standard of care in pediatrics. Surgical interventions including video-assisted thoracoscopic surgery (VATS) done by an experienced surgeon may reduce morbidity and shorten the length of hospital stay. The therapeutic choice will vary depending on the resources available and the preferences of the clinician.

Prognosis

The prognosis is related to the severity of disease but is generally excellent, with complete or nearly complete recovery in most instances.

VIRAL PNEUMONIA

Viral infection is a common cause of CAP in children. Viral pneumonia is most common in children younger than 2 years. Respiratory syncytial virus (RSV), human rhinovirus, adenovirus, parainfluenza (types 1–3), influenza (A and B) viruses, coronavirus, and human metapneumovirus are responsible for the large majority of cases. Severity of disease, severity of fever, radiographic findings, and the characteristics of cough or lung sounds do not reliably differentiate viral from bacterial pneumonias. Furthermore, viral infections may predispose to bacterial pneumonia. However, substantial pleural effusions, pneumatoceles, abscesses, lobar consolidation with lobar volume expansion, and “round” pneumonias are generally inconsistent with viral disease.

Clinical Findings

A. Symptoms and Signs

An upper respiratory infection frequently precedes the onset of lower respiratory disease due to viruses. Although wheezing or stridor may be prominent in viral disease, other findings, such as cough, signs of respiratory distress (tachypnea, retractions, grunting, and nasal flaring), and physical findings (rales and decreased breath sounds), are similar to those in bacterial pneumonia.

B. Laboratory Findings

Rapid viral diagnostic methods such as fluorescent antibody tests, enzyme-linked immunosorbent assay, and/or PCR should only be performed on nasopharyngeal secretions if the result will change management, is necessary a viral etiology in high-risk patients, or is required for epidemiology or infection control. The peripheral white blood cell count is not useful in distinguishing viral from bacterial disease.

C. Imaging Studies

Chest radiographs frequently show perihilar streaking, increased interstitial markings, peribronchial cuffing, or patchy bronchopneumonia. Lobar consolidation or atelectasis may occur, however. Hyperinflation of the lungs may occur when involvement of the small airways is prominent.

Differential Diagnosis

The differential diagnosis of viral pneumonia is the same as for bacterial pneumonia. Patients with prominent wheezing may have asthma, airway obstruction caused by foreign-body aspiration, and acute bacterial or viral tracheitis.

Complications

Viral pneumonia or laryngotracheobronchitis may predispose the patient to subsequent bacterial tracheitis or pneumonia as immediate sequelae. Bronchiolitis obliterans or severe chronic respiratory failure may follow adenovirus pneumonia. The results of studies evaluating the development of asthma after a viral pneumonia are variable. Bronchiectasis, chronic hypersensitivity pneumonia and unilateral hyperlucent lung (Sawyer-James syndrome) may follow measles, adenovirus, and influenza pneumonias.

Treatment

General supportive care for viral pneumonia does not differ from that for bacterial pneumonia. Patients can be quite ill and should be hospitalized according to the level of their illness. Because bacterial disease often cannot be definitively excluded, antibiotics may be indicated.

Patients at risk for life-threatening RSV infections (eg, those with BPD or other severe pulmonary conditions, congenital heart disease, or significant immunocompromise) should be hospitalized and ribavirin should be considered. Rapid viral diagnostic tests may be a useful guide for such therapy.

All children with influenza should be treated with the appropriate therapy for the specific type of influenza (A, B, H1N1). When available epidemiologic data indicate an active influenza infection in the community, antiviral therapy should be considered early for high-risk infants and children who appear to be infected. For dosing recommendations, refer to the American Academy of Pediatrics (AAP) 2018 Redbook. Children with suspected viral pneumonia should be placed in respiratory isolation.

Prognosis

Although most children with viral pneumonia recover uneventfully, worsening asthma, abnormal pulmonary function or chest radiographs, persistent respiratory insufficiency, and even death may occur in high-risk patients such as newborns or those with underlying lung, cardiac, or immunodeficiency disease. Patients with coinfections, virus-virus coinfections, or virus-bacterium co-infections have worse outcomes.

BRONCHIOLITIS

Bronchiolitis is the most common serious acute respiratory illness in infants and young children. The diagnosis of bronchiolitis is based on clinical findings including an upper respiratory infection that has progressed to cough, tachypnea, respiratory distress, and crackles or wheeze by physical examination. In most literature from the United States, this definition of bronchiolitis specifically applies to children younger than 2 years. One to 3% of infants with bronchiolitis will require hospitalization, especially during the winter months. Respiratory syncytial virus (RSV) is by far the most common viral cause of acute bronchiolitis. Parainfluenza, human metapneumovirus, influenza, and adenovirus are less common causes of bronchiolitis during early infancy.

Prevention

The most effective preventions against RSV infection are proper handwashing techniques and reducing exposure to potential environmental risk factors. Prophylaxis with a monoclonal antibody (palivizumab) is effective at reducing the rate of hospitalization and associated morbidity in high-risk premature infants and those with chronic cardiopulmonary conditions. Dosing recommendations in the United States are available in the AAP 2018 Redbook.

Clinical Findings

A. Symptoms and Signs

The usual course of RSV bronchiolitis is 1–2 days of fever, rhinorrhea, and cough, followed by wheezing, tachypnea, and respiratory distress. Typically, the breathing pattern is shallow, with rapid respirations. Nasal flaring, cyanosis, retractions, and rales may be present, along with prolongation of the expiratory phase and wheezing, depending on the severity of illness. Some young infants present with apnea and few findings on auscultation but may subsequently develop rales, rhonchi, and expiratory wheezing.

B. Laboratory Findings and Imaging Studies

A nasal wash can be used to identify the causative pathogen but is not necessary to make the diagnosis of bronchiolitis. The peripheral white blood cell count may be normal or show a mild lymphocytosis. Chest radiographs are not indicated in children who have bilateral, symmetrical findings on examination, who are not in significant respiratory distress, and who do not have elevated temperature. Chest radiograph findings are generally nonspecific and typically include hyperinflation, peribronchial cuffing, increased interstitial markings, and subsegmental atelectasis.

Complications

Bacterial superinfection is a rare complication of viral pneumonia. The results of studies investigating the risk for the subsequent development of chronic airway hyperreactivity (asthma) are variable. Bronchiolitis due to RSV infection contributes substantially to morbidity and mortality in children with underlying medical disorders, including chronic lung disease of prematurity, CF, congenital heart disease, and immunodeficiency.

Treatment

Although most children with RSV bronchiolitis are readily treated as outpatients, hospitalization is required in infected children with hypoxemia on room air, a history of apnea, moderate tachypnea with feeding difficulties, and marked respiratory distress with retractions. Children at high risk for hospitalization include infants (aged < 6 months), especially with any history of prematurity, and those with underlying chronic cardiopulmonary disorders. While in the hospital, treatment should include supportive strategies such as frequent suctioning and providing adequate fluids to maintain hydration. If hypoxemia is present, supplemental oxygen should be administered. There is no evidence to support the use of antibiotics in children with bronchiolitis unless there is evidence of an associated bacterial pneumonia. Bronchodilators and corticosteroids have not been shown to change the severity or the length of the illness in bronchiolitis and therefore are not recommended. Studies evaluating the effectiveness of hypertonic saline and heated high-flow oxygen therapy are ongoing.

Patients at risk for life-threatening RSV infections (eg, children born at < 35 weeks, children with other severe pulmonary conditions, congenital heart disease, neuromuscular disease, or significant immunocompromise) should be considered for RSV prophylaxis therapy. For more detail, refer to the AAP 2018 Redbook. High-risk patients with RSV bronchiolitis may need to be hospitalized and treated with ribavirin.

Prognosis

The prognosis for most infants with acute bronchiolitis is very good. With improved supportive care and prophylaxis with palivizumab, the mortality rate among high-risk infants has decreased substantially.

MYCOPLASMA PNEUMONIA

M pneumoniae is a common cause of symptomatic pneumonia in older children although it may be seen in children younger than 5 years. Endemic and epidemic infection can occur. The incubation period is long (2–3 weeks), and the onset of symptoms is slow. Although the lung is the primary infection site, extrapulmonary complications sometimes occur. Extrapulmonary complications in CAP suggest the diagnosis of M. pneumoniae.

Clinical Findings

A. Symptoms and Signs

Fever, cough, headache, and malaise are common symptoms as the illness evolves. Although cough is usually dry at the onset, sputum production may develop as the illness progresses. Sore throat, otitis media, otitis externa, and bullous myringitis may occur. Rales and chest pain are frequently present on chest examination; decreased breath sounds or dullness to percussion over the involved area may be present.

B. Laboratory Findings and Imaging Studies

PCR is the gold standard for diagnosis. However, like other respiratory pathogens, Mycoplasma can be carried in the upper respiratory tract after resolution of active infection. Enzyme immunoassay (EIA) and complement fixation are sensitive and specific for M pneumoniae but may also be positive in asymptomatic children. Serologic (IgG) testing collected over 2 weeks showing a fourfold or greater rise in specific antibodies confirms the diagnosis of active respiratory disease due to M pneumoniae. The total and differential white blood cell counts are usually normal.

Chest radiographs usually demonstrate interstitial or bronchopneumonic infiltrates, frequently in the middle or lower lobes. Pleural effusions are extremely uncommon.

Complications

Extrapulmonary involvement of the blood, central nervous system, skin, heart, or joints can occur. Direct Coombs–positive autoimmune hemolytic anemia, occasionally a life-threatening disorder, is the most common hematologic abnormality that can accompany M pneumoniae infection. Coagulation defects and thrombocytopenia can also occur. Cerebral infarction, meningoencephalitis, Guillain-Barré syndrome, cranial nerve involvement, and psychosis all have been described. A wide variety of skin rashes, including erythema multiforme and Stevens-Johnson syndrome, can occur. Bronchiolitis obliterans due to Stephens-Johnson syndrome associated with M pneumoniae also has been reported.

Treatment

Antibiotic therapy with a macrolide for 7–10 days may shorten the course of illness. Ciprofloxacin is a possible alternative. Supportive measures, including hydration, antipyretics, and bed rest, are helpful.

Prognosis

In the absence of the less common extrapulmonary complications, the outlook for recovery is excellent.

ASPIRATION PNEUMONIA

Patients whose anatomic defense mechanisms are impaired are at risk of aspiration pneumonia (Table 19–6). Aspiration pneumonia may be acute or chronic but is more common in children with other underlying medical conditions (see Table 19–6). An acute aspiration event may lead to a typical pneumonia syndrome with fever, asymmetrical auscultation findings, and asymmetric imaging findings. Chronic aspiration pneumonitis is more indolent and can cause chronic respiratory symptoms of “rattling,” cough or wheezing, chronic chest infiltrates, bronchiectasis, or failure to thrive. Pneumonitis is worsened by gram-negative anaerobes and other bacteria present in the mouth.

Clinical Findings

A. Symptoms and Signs

Acute onset of fever, cough, respiratory distress, or hypoxemia in a patient at risk suggests acute aspiration pneumonia. Chest physical findings, such as rales, rhonchi, or decreased breath sounds, may initially be limited to the lung region into which aspiration occurred. Although any region may be affected, the right side—especially the right upper lobe in the supine patient—is commonly affected. In patients with chronic aspiration “chest rattling” is often described by parents. Generalized rales and wheezing may also be present.

B. Laboratory Findings and Imaging Studies

Chest radiograph abnormalities can vary widely. They may reveal lobar consolidation or atelectasis and focal or generalized alveolar or interstitial infiltrates. Complications such as empyema or lung abscess may complicate acute aspiration pneumonia. In some patients with chronic aspiration, perihilar infiltrates with or without bronchiectasis may be seen. If there is clinical concern, chest CT can better delineate these complications.

In patients with chronic aspiration pneumonitis, attempts should be made to evaluate dysphagia. VFSS is typically performed to evaluate the swallow. Fiberoptic endoscopic examination of swallowing (FEES) is done at specialty centers to directly visualize the larynx during swallowing via laryngoscope. Radionuclide studies have low sensitivity to diagnosis aspiration. Although biomarkers such as lipid-laden macrophages obtained from BAL samples have low sensitivity and specificity, BAL may be considered to diagnose bacterial infection (see section Diagnosis of Respiratory Tract Infections). Anatomic abnormalities such as laryngeal cleft can be evaluated by rigid laryngoscopy/bronchoscopy. Tracheoesophageal fistula is rare and can be difficult to diagnose: UGI fluoroscopy series, rigid or flexible bronchoscopy, or esophageal endoscopy may aid in diagnosis. The role of esophageal disease, gastroesophageal reflux, and impaired esophageal motility in chronic aspiration may warrant evaluation by a gastroenterologist or multidisciplinary aerodigestive team.

Differential Diagnosis

In the acutely ill patient, bacterial and viral pneumonias should be considered. In the chronically ill patient, the differential diagnosis may include disorders causing recurrent pneumonia (eg, immunodeficiencies, ciliary dysfunction, or foreign body), chronic wheezing, or interstitial lung disorders (see the next section), depending on the presentation.

Treatment

Aspiration pneumonia leads to a chemical pneumonitis, and supportive treatment is recommended. Antimicrobial therapy for patients who are acutely ill from aspiration pneumonia includes coverage for anaerobic organisms. In general, clindamycin is appropriate initial coverage.

Treatment of chronic aspiration pneumonitis may include the following: surgical correction of anatomic abnormalities; paced swallowing systems/bottles, thickening of liquids taken by mouth, swallowing therapy, improved oral hygiene, inhaled corticosteroids, and chest physiotherapy. In patients with compromise of the central nervous system, exclusive feeding by gastrostomy may be required. Because of the widespread causes and consequences of chronic aspiration, multidisciplinary aerodigestive management is often recommended.

PNEUMONIA IN THE IMMUNOCOMPROMISED HOST

Compromised immune function occurs following solid organ or hematopoietic stem cell transplantation, in patients with congenital immune deficits, and in patients receiving cancer chemotherapy or other immunosuppressant therapy, including chronic corticosteroids.

Pulmonary infection, which is the most common infection in these patients, can present as focal pneumonia, pulmonary nodules, disseminated disease, or diffuse ILD. The underlying cause of the immunocompromised state often determines the spectrum of infectious agents responsible for disease (see also Chapter 33). Pneumonia in an immunocompromised host may be due to any common community-acquired bacteria or less common pathogens such as opportunistic fungi, Toxoplasma gondii, P jiroveci, anaerobic bacteria, Nocardia species, Legionella pneumophila, mycobacteria, and viruses. Multiple organisms are commonly isolated in culture.

Clinical Findings

A. Symptoms and Signs

Patients often present with subtle signs such as mild cough, tachypnea, or low-grade fever that can rapidly progress to high fever, respiratory distress, and hypoxemia or Children’s Interstitial and diffuse Lung Disease (chILD) syndrome. An obvious portal of infection, such as an intravascular catheter, may predispose to bacterial or fungal infection via hematogenous spread.

B. Laboratory Findings and Imaging Studies

Fungal, parasitic, or bacterial infection, especially with antibiotic-resistant bacteria, should be suspected in the neutropenic child. Cultures of peripheral blood and through intravascular catheters, sputum, tracheobronchial secretions, nasopharynx or sinuses, pleural fluid, biopsied lymph nodes, bone marrow, or skin lesions should be considered and obtained as soon as infection is suspected. Serum (1, 3)-β-d-glucan assays and serum and BAL galactomannan assays for invasive pulmonary fungal disease are being used in some centers. Urine can be tested for typical pathogens and Legionella urinary antigens.

Invasive methods are commonly required to make a diagnosis. Appropriate samples should be obtained soon after a patient with pneumonia fails to respond to initial treatment. The results of these procedures usually lead to important changes in empiric therapy. Sputum is often unavailable in the young child. BAL frequently detects one or more organisms and should be done early in evaluation. The combined use of a wash, brushing, endobronchial biopsy, and lavage has a high yield. In patients with rapidly advancing, or more peripheral disease, lung biopsy becomes more urgent. The morbidity and mortality of this procedure can be reduced by VATS techniques.

Because of the multiplicity of organisms that may cause disease, a comprehensive set of studies should be done on lavage and biopsy material. These consist of rapid diagnostic studies including culture, PCR, and antigen detection for viruses and rapid fluorescent antibody studies for P jiroveci and Legionella; Gram, acid-fast, and fungal stains; cytologic examination for viral inclusions; and cultures for anaerobic and aerobic bacteria, fungi, mycobacteria, and Legionella.

Chest radiographs and volumetric CT scans may be useful in identifying the pattern and extent of disease. In early P jiroveci pneumonia, dyspnea and hypoxemia may be marked despite minimal radiographic abnormalities. Distinctive radiographic findings such as the halo sign can be seen in aspergillosis.

Differential Diagnosis

The organisms causing disease vary with the type of immunocompromise present. For example, the splenectomized or sickle cell disease patient may be overwhelmed by infection with encapsulated bacteria. The child with HIV/AIDS or receiving immunosuppressant therapy or chemotherapy is more likely to have P jiroveci infection. The febrile neutropenic child who has been receiving adequate doses of intravenous broad-spectrum antibiotics or systemic steroid therapy may have fungal disease. The key to diagnosis is to consider all possibilities of infection.

Depending on the form of immunocompromise, perhaps only one-half to two-thirds of new pulmonary infiltrates in such patients represent infection. The remaining infiltrates are caused by pulmonary toxicity of radiation, chemotherapy, or other drugs; pulmonary disorders, including hemorrhage, embolism, atelectasis, or aspiration; idiopathic pneumonia syndrome or acute respiratory distress syndrome in bone marrow transplant patients; recurrence or extension of primary malignant growths or immunologic disorders; transfusion reactions, leukostasis, or tumor cell lysis; or ILD, such as lymphocytic interstitial pneumonitis with HIV infection.

Complications

Necrotizing pneumonia, lung abscess, and parapneumonic effusions can develop. Progressive respiratory failure, shock, multiple organ damage, disseminated infection, and death commonly occur in the infected immunocompromised host.

Treatment

Early use of broad-spectrum intravenous antibiotics is indicated in febrile, neutropenic, or immunocompromised children. Trimethoprim-sulfamethoxazole (for P jiroveci), macrolides (for Legionella) are/or antifungals may also be indicated early in the treatment of immunocompromised children before an organism is identified. Targeted therapy should be based on studies of specimens obtained from BAL or lung biopsy. Recent data suggest that use of noninvasive ventilation strategies early in the course of pulmonary insufficiency or respiratory failure may decrease mortality.

Prognosis

Prognosis is based on the severity of the underlying immunocompromise, appropriate early diagnosis and treatment, and the infecting organisms. Intubation and mechanical ventilation have been associated with high mortality, especially in hematopoietic stem cell transplant patients.

LUNG ABSCESS

Pathogenesis

Lung abscesses are thick-walled cavities that form from inflammation and central necrosis following an initial pulmonary infection. A lung abscess can occur in a previously well child, a child prone to aspiration, or in children with immunosuppression or underlying lung or systemic disease. Lung abscesses may also occur via embolic spread. Organisms such as staphylococci and streptococci more commonly affect the healthy host, while anaerobic and gram-negative organisms as well as Nocardia, mycobacteria, Legionella species, fungi (Candida and Aspergillus), and drug-resistant pathogens should be considered in the immunocompromised host or in patients not responding to typical antibiotic treatment.

Clinical Findings

A. Symptoms and Signs

Symptoms and signs referable to the chest may or may not be present. High fever, malaise, and weight loss are often present. In infants, evidence of respiratory distress can be present.

B. Laboratory Findings and Imaging Studies

Elevated peripheral white blood cell count with a neutrophil predominance or an elevated erythrocyte sedimentation rate or CRP may be present. Blood cultures are rarely positive except in the immunocompromised patient.

Chest radiographs usually reveal single or multiple thick-walled lung cavities, often with air-fluid levels. Local compressive atelectasis, pleural thickening, or adenopathy may also occur. Chest CT scan may provide better localization and understanding of the lesions.

In patients producing sputum, stains, and cultures may provide the diagnosis. Direct percutaneous aspiration of material for stains and cultures should be considered although complications can occur.

Differential Diagnosis

Loculated pyopneumothorax, neoplasms, plasma cell granuloma, and infected congenital cysts and sequestrations should be considered. Pneumatoceles, non–fluid-filled cysts, are common in children with empyema and usually resolve over time.

Complications

Although complications due to abscesses are now rare, mediastinal shift, tension pneumothorax, and spontaneous rupture can occur. Diagnostic maneuvers such as radiology-guided lung puncture to drain and culture the abscess may also cause pneumothorax or a bronchopulmonary fistula.

Treatment

Because of the risks of lung puncture, uncomplicated abscesses are frequently conservatively treated in the immune competent host with appropriate broad-spectrum intravenous antibiotics. Additional coverage for anaerobic gram-negative organisms and fungi should be provided for others. Prolonged therapy with 2–3 weeks of intravenous antibiotics followed by oral therapy may be required. Attempts to drain abscesses via bronchoscopy have caused life-threatening airway compromise. Surgical drainage or lobectomy is occasionally required, primarily in immunocompromised patients. However, such procedures may themselves cause life-threatening complications.

Prognosis

Although radiographic resolution may be very slow (6 weeks–5 years), resolution occurs in most patients without risk factors for lower respiratory tract infections or loss of pulmonary function. In the immunocompromised or medically complex host, the outlook depends on the underlying disorder.

Bronchiolitis obliterans is a rare chronic obstructive lung disease characterized by complete obliteration of the small airways following a severe insult. The most common etiology in children is post-infectious, following a lower airway tract infection with adenovirus, although influenza, rubeola, Bordetella, and Mycoplasma are also implicated. Other causes include connective tissue diseases, chronic aspiration, Stevens-Johnson syndrome, posttransplantation (lung or bone marrow), and inhalational injury. Many cases of bronchiolitis obliterans are idiopathic. Mechanical ventilation for severe adenoviral respiratory infection is a strong risk factor for development of bronchiolitis obliterans.

Clinical Findings

A. Symptoms and Signs

Persons with bronchiolitis obliterans usually experience dyspnea, coughing, and exercise intolerance. This diagnosis should be considered in children with persistent cough, wheezing, crackles, or hypoxemia lasting longer than 60 days following a lower respiratory tract infection.

B. Laboratory Findings and Imaging Studies

Chest radiograph abnormalities include evidence of heterogeneous air trapping and airway wall thickening. Traction bronchiectasis can occur as the disease progresses. Classic findings on chest CT include a mosaic perfusion pattern, vascular attenuation, and central bronchiectasis. After hematopoietic stem cell transplantation, bronchiectasis may not be present. This finding along with pulmonary function testing showing airway obstruction unresponsive to bronchodilators may be diagnostic in patients with the appropriate clinical history. Although not typically required for diagnosis, ventilation-perfusion scans may show a pattern of ventilation and perfusion mismatch. Pulmonary angiograms reveal decreased vasculature in involved lung, and bronchograms show marked pruning of the bronchial tree. Lung biopsy is necessary typically only in cases where clinical history and/or CT scan are not classic. Pathologic findings include airway scarring (eg, with fibrin) with partial or complete obstruction of bronchioles.

Differential Diagnosis

Poorly treated asthma with remodeling, CF, and BPD must be considered in children with persistent airway obstruction. A trial of medications (including bronchodilators and corticosteroids) may help determine the reversibility of the process when the primary differential is between asthma and bronchiolitis obliterans. Others without classic findings on CT scan and lung function testing may require a lung biopsy.

Complications

Sequelae of bronchiolitis obliterans include persistent airway obstruction, recurrent wheezing, bronchiectasis, chronic atelectasis, recurrent pneumonia, and unilateral hyperlucent lung syndrome.

Treatment

Supportive care, including supplemental oxygen for hypoxemia, routine vaccination, avoidance of environmental irritant exposure, exercise, and nutritional support should be provided. Ongoing airway damage due to problems such as aspiration should be prevented. Inhaled bronchodilators (β-agonists and anticholinergic) may reverse airway obstruction if the disease has a reactive component. Systemic corticosteroids may help reverse the obstruction or prevent ongoing damage; these can be given orally or with monthly intravenous doses (intravenous doses may decrease systemic side effects). Azithromycin is beneficial in bronchiolitis obliterans syndrome after lung transplantation and in patients with bronchiectasis. Fluticasone, azithromycin, and montelukast have been used to treat bronchiolitis obliterans after hematopoietic stem cell transplantation. There are concerns for disease recurrence (ie, leukemia) with prophylactic use of azithromycin. Lung transplant may be an option for patients with severe, progressive disease. If bronchiectasis is present, airway clearance and early antibiotics with respiratory illnesses (ie, to treat endobronchitis) are helpful.

Prognosis

Prognosis depends in part on the underlying cause as well as the age of onset. Postinfectious bronchiolitis obliterans tends to be nonprogressive with low mortality and the possibility of slow improvement. Conversely, posttransplantation or Stevens-Johnson syndrome–related bronchiolitis obliterans may have a rapidly progressive course leading to death or need for lung transplantation.

CHILDREN’S INTERSTITIAL LUNG DISEASE SYNDROME

Children’s Interstitial and diffuse Lung Disease (chILD) syndrome describes a constellation of signs and symptoms and not a specific diagnosis (Table 19–7). Once recognized, chILD syndrome should elicit a search for a more specific diagnosis. More common pulmonary diseases that can present similarly to chILD should be evaluated and excluded first, including CF, cardiac disease, asthma, acute infection, immunodeficiency, neuromuscular disease, thoracic cage abnormality, chronic lung disease of prematurity, and aspiration.

Clinical Findings

A. Symptoms and Signs

chILD presents acutely in infants and young children with respiratory failure and inability to wean supplemental O₂ or alternatively insidiously with cough, exercise intolerance, clubbing, dyspnea, tachypnea, retractions, hypoxemia, barrel chest, and failure to thrive. Crackles are common on chest auscultation.

B. Laboratory Findings

After a comprehensive history and examination, initial evaluation may include PFTs, allergy skin tests, complete blood count with WBC differential, CRP and erythrocyte sedimentation rate (ESR), and comprehensive metabolic panel. Cardiac evaluation including an electrocardiogram and echocardiogram should be obtained. Immunologic assessment includes serum immunoglobulins and markers of collagen vascular disease. DNA analysis for surfactant protein dysfunction syndromes is done commonly in young children.

C. Imaging Studies

Chest radiographs are normal in up to 10%–15% of patients, but volumetric CT scans are always abnormal. Certain specific chILD disorders such as bronchiolitis obliterans and neuroendocrine cell hyperplasia of infancy can be diagnosed by characteristic CT findings alone.

D. Special Tests

Pulmonary function testing is typically abnormal in chILD. Depending on the specific type of chILD, PFTs may show (1) a restrictive pattern of decreased lung volumes, compliance, and carbon monoxide diffusing capacity, (2) an obstructive pattern with hyperinflation, or (3) a mixed obstructive-restrictive pattern. Six-minute walk test often demonstrates SpO₂ desaturation and reduced distance capacity. Exercise-induced or nocturnal hypoxemia may be the earliest physiologic abnormality in chILD.

Bronchoscopy can exclude anatomic abnormalities and obtain BAL for microbiologic and cytologic testing but is seldom diagnostic alone. Commercial genetic testing is available for surfactant dysfunction mutations (SFTPB, SFTPC, ABCA3, and NKX2.1), alveolar capillary dysplasia (FOXF1), pulmonary alveolar proteinosis (GMCSF receptor mutations or autoantibodies), and pulmonary hemorrhage (COPA). Lung biopsy is often required for a definitive diagnosis, and video-assisted thoracoscopically lung biopsies are preferred.

Differential Diagnosis

Many disorders have similar presentations: CF cardiac disease, asthma, acute infection, immunodeficiency, neuromuscular disease, scoliosis, thoracic cage abnormality, chronic lung disease of prematurity, and aspiration.

Complications

Complications from chILD include being behind in school, failure to thrive, respiratory insufficiency, respiratory failure, and pulmonary hypertension. Mortality and morbidity can be significant and varies by specific diagnosis.

Treatment

The mainstays of treatment include support with supplemental O₂ and nutritional support. Corticosteroids are used for many of the specific chILD diagnoses as well as other disease specific medications. Patients with severe disease may need noninvasive respiratory support. All patients should be evaluated for comorbidities such as pulmonary hypertension, aspiration, failure to thrive, sleep apnea and hypoxemia. All vaccines should be provided, including annual influenza vaccine, palivizumab in infancy, and pneumococcal polysaccharide vaccine. Nutritional and respiratory support should be provided as appropriate to encourage optimal growth and development. Environmental irritant exposure (recreational and occupational) should be avoided. Most treatment for chILD is disease specific and based on expert opinion, case reports, and small case series. Children with chILD should be evaluated and cared for by an experienced multidisciplinary team. Lung transplantation may be an option for patients with progressive respiratory failure. The chILD Family Foundation can provide further supportive resources for families (http://www.childfoundation.us).

Prognosis

Prognosis varies by chILD diagnosis from mild disease to progressive respiratory failure and death.

HYPERSENSITIVITY PNEUMONITIS

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a T-cell–mediated disease involving the peripheral airways, interstitium, and alveoli. The disease is triggered by the host response to an environmental exposure. Both acute and chronic forms may occur. In children, the most common antigen(s) are birds or bird droppings (eg, pigeons, parakeets, parrots, or doves); this is also known as “bird fancier’s lung.” However, a multitude of antigens have been documented to cause HP, including moldy hay, compost, logs or tree bark, sawdust, or aerosols from humidifiers or hot tubs. Methotrexate-induced hypersensitivity has also been described in a child with juvenile rheumatoid arthritis. Hot tub lung can be caused by exposure to aerosolized Mycobacterium avium complex. A high level of suspicion and a thorough environmental exposure history are required for diagnosis.

Clinical Findings

A. Symptoms and Signs

Episodic cough and fever can occur following acute exposures. Chronic exposure results in weight loss, fatigue, hypoxemia, and dyspnea. Physical examination findings include crackles, loud cardiac P2, and clubbing.

B. Laboratory Findings and Imaging Studies

Acute exposure may cause polymorphonuclear leukocytosis with eosinophilia and airway obstruction or restriction on lung function testing. Chronic HP results in a restrictive pattern.

Serum precipitins (precipitating IgG antibodies) to the triggering antigen may be detected, but perhaps only if the identical antigen is used. The cell counts on BAL typically show lymphocytosis. Chest radiograph findings are variable and may include normal lung fields, air-space consolidation, and linear nodular or reticulonodular opacities. Chest CT often shows small centrilobular nodules, ground-glass opacities, and air-trapping. Chronic HP may progress to pulmonary fibrosis.

Lung biopsy reveals bronchiolocentric interstitial lymphocytic inflammation interstitial nonnecrotizing, poorly formed granulomas, and intraalveolar foci of organizing pneumonia.

Differential Diagnosis

Patients with acute symptoms must be differentiated from acute asthma exacerbations. Patients with chronic symptoms must be distinguished from chILD due to collagen-vascular, immunologic dysfunction, or other forms of chILD.

Complications

Prolonged exposure to offending antigens may result in pulmonary hypertension due to chronic hypoxemia, irreversible restrictive lung disease, and pulmonary fibrosis.

Treatment & Prognosis

The primary goal is complete elimination of exposure to the offending antigen. Corticosteroids treatment is controversial. With early diagnosis and avoidance of offending antigens, the prognosis is excellent.

PULMONARY HEMORRHAGE

Pulmonary hemorrhage can be caused by a spectrum of disorders affecting the large and small airways and alveoli. It can occur as an acute or chronic process. If pulmonary hemorrhage is subacute or chronic, hemosiderin-laden macrophages can be found in tracheal aspirates 48–72 hours after the bleeding begins. Many cases are secondary to bacterial, mycobacterial, parasitic, viral, or fungal infections (such as the toxigenic mold Stachybotrys chartarum). Lung abscess, bronchiectasis (from CF or other causes), foreign body, coagulopathy (often with overwhelming sepsis), or elevated pulmonary venous pressure (secondary to congestive heart failure, anatomic heart lesions, or ascent to high altitude) may also cause pulmonary hemorrhage. Other causes include lung contusion from trauma, pulmonary embolus with infarction, arteriovenous fistula or telangiectasias, autoimmune vasculitis, HP pulmonary sequestration, agenesis of a single pulmonary artery, and esophageal duplication or bronchogenic cyst. In children, pulmonary hemorrhage due to airway tumors (eg, bronchial adenoma) is very rare.

Hemorrhage involving the alveoli is termed diffuse alveolar hemorrhage. This may be idiopathic, drug-related, or may occur in Goodpasture syndrome, rapidly progressive glomerulonephritis, and systemic vasculitides (often associated with such collagen-vascular diseases as systemic lupus erythematosus, rheumatoid arthritis, Wegener granulomatosis, polyarteritis nodosa, Henoch-Schönlein purpura, and Behçet disease). Idiopathic pulmonary hemosiderosis refers to the accumulation of hemosiderin in the lung, especially in alveolar macrophages, as a result of chronic or recurrent hemorrhage (usually from pulmonary capillaries) that is not associated with the previously listed causes. Children and young adults are mainly affected, with the age at onset ranging from 6 months to 20 years.

Clinical Findings

A. Symptoms and Signs

Large airway hemorrhage presents with hemoptysis and symptoms of the underlying cause, such as infection, foreign body, or bronchiectasis in CF. Hemoptysis from larger airways is often bright red or contains clots. Children with diffuse alveolar hemorrhage may present with massive hemoptysis, marked respiratory distress, stridor, or a pneumonia-like syndrome. However, most patients with diffuse alveolar hemorrhage and idiopathic pulmonary hemosiderosis present with nonspecific respiratory symptoms (cough, tachypnea, and retractions) with or without hemoptysis, poor growth, and fatigue. Fever, abdominal pain, and chest pain may also be reported. Jaundice and hepatosplenomegaly may be present with chronic bleeding. Physical examination often reveals decreased breath sounds, rales, rhonchi, or wheezing and digital clubbing.

B. Laboratory Findings and Imaging Studies

Laboratory studies depend on the cause of hemorrhage. When gross hemoptysis is present, large airway bronchiectasis, epistaxis, foreign body, and arteriovenous malformations should be considered. Flexible bronchoscopy and imaging (MRI or CT-assisted angiography) can be used to localize the site of bleeding. Alveolar bleeding with hemoptysis is often frothy and pink. Long-standing idiopathic pulmonary hemorrhage may cause iron deficiency anemia and heme-positive sputum. Nonspecific findings may include lymphocytosis and an elevated erythrocyte sedimentation rate. Peripheral eosinophilia is present in up to 25% of patients. Chest radiographs may demonstrate perihilar infiltrates, fluffy alveolar infiltrates with or without atelectasis, and mediastinal adenopathy. Pulmonary function testing generally reveals restrictive impairment, with low lung volumes, poor compliance, and an increased diffusion capacity. Hemosiderin-laden macrophages are found in the BAL fluid and tracheal aspirates. The diagnostic usefulness of lung biopsy is controversial.

Patients with diffuse alveolar hemorrhage with an underlying systemic disease may need a lung biopsy. In patients with systemic lupus erythematosus, granulomatosis and polyangiitis (formerly called Wegener granulomatosis), and occasionally Goodpasture syndrome diffuse alveolar hemorrhage can occur in the setting of necrotizing pulmonary capillaritis. Lung biopsy reveals alveolar septa infiltrated with neutrophils, edema, or necrosis in addition to alveolar hemorrhage. Idiopathic pulmonary hemosiderosis is a mild form of capillaritis associated with focal or diffuse alveolar hemorrhage. Other causes of pulmonary hemosiderosis include collagen-vascular disease, immune-mediated vasculitis, and pulmonary fibrosis must be ruled out to diagnose idiopathic pulmonary hemosiderosis. Lung biopsy often shows immune-mediated capillaritis in the absence of an identifiable serologic marker. Serologic studies such as circulating antineutrophilic cytoplasmic autoantibodies for Wegener granulomatosis, perinuclear antineutrophilic cytoplasmic autoantibodies for microscopic polyangiitis, antinuclear antibodies for systemic lupus erythematosus, and anti–basement membrane antibodies for Goodpasture syndrome should be obtained. α₁-Antitrypsin deficiency should also be considered.

Cow’s milk-induced pulmonary hemosiderosis (Heiner syndrome) can be confirmed by high titers of serum precipitins to multiple constituents of cow’s milk and positive intradermal skin tests to cow’s milk proteins. Improvement after eliminating cow’s milk supports the diagnosis.

Differential Diagnosis

Bleeding from the nose or mouth can present as hemoptysis. Therefore, a complete examination of the nose and mouth is required before confirming the diagnosis of intrapulmonary bleeding. Hematemesis can also be confused with hemoptysis; confirming that the blood was produced after coughing and not with emesis should also be part of the initial evaluations. A complete past medical history including underlying systemic illness and cardiovascular anomalies may direct the search for the site of respiratory bleeding.

Treatment

Therapy should be aimed at direct treatment of the underlying disease. In severe bleeding, intubation with application of positive pressure during mechanical ventilation and/or endotracheal administration of epinephrine may help attenuate bleeding. Patients with CF or bronchiectasis from other causes who develop massive (> 240 mL) or recurrent hemoptysis may require bronchial artery embolization. Although its use requires anticoagulation, extracorporeal life support has resulted in the survival of children with severe pulmonary hemorrhage. For chronic bleeding, supportive measures, including iron therapy, supplemental oxygen, and blood transfusions, may be needed. A diet free of cow’s milk should be tried in infants. Systemic corticosteroids have been used for various causes of diffuse alveolar hemorrhage and have been particularly successful in those secondary to collagen-vascular disorders and vasculitis. Case reports have been published describing the variable effectiveness of steroids, chloroquine, cyclophosphamide, and azathioprine for idiopathic pulmonary hemosiderosis.

Prognosis

The outcome of pulmonary hemorrhage depends on the cause of the bleeding and how much blood has been lost. The course of idiopathic pulmonary hemosiderosis is variable, characterized by a waxing and waning course of intermittent intrapulmonary bleeds and the gradual development of pulmonary fibrosis. The severity of the underlying renal disease influences mortality associated with Goodpasture syndrome and Wegener granulomatosis. Diffuse alveolar hemorrhage is considered a lethal pulmonary complication of systemic lupus erythematosus.

PULMONARY EMBOLISM

Pulmonary embolism is a rare, but severe cause of respiratory distress in children. Etiologies include sickle cell anemia (as part of the acute chest syndrome), malignancy, rheumatic fever, infective endocarditis, bone fracture, dehydration, polycythemia, nephrotic syndrome, atrial fibrillation, and other conditions. Many children with pulmonary emboli referred for hematology evaluation have coagulation regulatory protein abnormalities and antiphospholipid antibodies. Emboli result in clinical signs and symptoms in proportion to the severity of pulmonary vascular obstruction. In children, tumor emboli are a more common cause of massive pulmonary embolism than embolization from a lower extremity deep venous thrombosis.

Clinical Findings

A. Symptoms and Signs

Pulmonary embolism usually presents as an acute onset of dyspnea and tachypnea. Heart palpitations, pleuritic chest pain, and a sense of impending doom may be reported.

Hemoptysis is rare but may occur along with splinting, cyanosis, and tachycardia. Massive emboli may be present with syncope and cardiac arrhythmias. Physical examination is usually normal (except for tachycardia and tachypnea) unless the embolism is associated with an underlying disorder. Mild hypoxemia, rales, focal wheezing, or a pleural friction rub may be found.

B. Laboratory Findings and Imaging Studies

Radiographic findings may be normal, but a peripheral infiltrate, small pleural effusion, or elevated hemidiaphragm can be present. If the emboli are massive, differential blood flow and pulmonary artery enlargement may be appreciated. The electrocardiogram is usually normal unless the pulmonary embolus is massive. Echocardiography is useful in detecting the presence of a large embolus in the great vessels. A negative D-dimer has a more than 95% negative predictive value for an embolus, but has poor specificity. Ventilation-perfusion scans show localized areas of ventilation without perfusion.

Spiral CT with contrast may be helpful, but pulmonary angiography is the gold standard. A recent case series suggests that bedside chest ultrasound may aid in diagnosing pulmonary emboli, particularly in critically ill children. Further evaluation may include Doppler ultrasound studies of the legs to search for deep venous thrombosis. Coagulation studies, including assessments of antithrombin III, fibrinogen, antiphospholipid antibodies, homocysteine, coagulation regulatory proteins (proteins C and S, and factor V Leiden), and the prothrombin G20210A mutation are abnormal in up to 70% of pediatric patients with pulmonary embolism.

Treatment

Acute treatment includes supplemental oxygen, and anticoagulation. Current recommendations include heparin therapy to maintain an activated partial thromboplastin time of greater than 1.5 times the control value for the first 24 hours. Urokinase or tissue plasminogen activator can be used to help dissolve the embolus. These therapies should be followed by warfarin therapy for at least 6 weeks with an international normalized ratio (INR) greater than 2.

PULMONARY EDEMA

Pathogenesis

Pulmonary edema is excessive accumulation of extravascular fluid in the lung. This occurs when fluid is filtered into the lungs faster than it can be removed, leading to changes in lung mechanics such as decreased lung compliance, worsening hypoxemia from ventilation-perfusion mismatch, bronchial compression, and if advanced, decreased surfactant function. There are two basic types of pulmonary edema: increased pressure (cardiogenic or hydrostatic) and increased permeability (noncardiogenic or primary). Hydrostatic pulmonary edema is usually due to excessive increases in pulmonary venous pressure, in the setting of congestive heart failure. Postobstructive pulmonary edema occurs when airway occlusion (or its sudden relief) causes a sudden drop in airway pressure that leads to increased venous return and decreased left heart blood flow. These changes result in elevated hydrostatic pressures and transudation of fluid from the pulmonary capillaries to the alveolar space.

In contrast, many lung diseases, especially acute respiratory distress syndrome, are characterized by the development of pulmonary edema secondary to changes in permeability due to injury at the alveolar-capillary interface. In this setting, pulmonary edema occurs independently of the elevations of pulmonary venous pressure.

Clinical Findings

A. Symptoms and Signs

Cyanosis, tachypnea, tachycardia, and respiratory distress are commonly present. Physical findings include rales, diminished breath sounds, and (in young infants) expiratory wheezing. More severe disease is characterized by progressive respiratory distress with marked retractions, dyspnea, and severe hypoxemia.

B. Imaging Studies

Chest radiographic findings depend on the cause of the edema. Pulmonary vessels are prominent, often with diffuse interstitial or alveolar infiltrates. Heart size is usually normal in permeability edema but enlarged in hydrostatic edema.

Treatment

Although specific therapy depends on the underlying cause, supplemental oxygen therapy and ventilator support may be indicated. Diuretics, digoxin, and vasodilators may be indicated for congestive heart failure along with restriction of salt and water. Loop diuretics, such as furosemide, are primarily beneficial because they increase systemic venous capacitance, not because they induce diuresis. Improvement can even be seen in anuric patients. Recommended interventions for pulmonary edema include reduction of vascular volume and maintenance of the lowest central venous or pulmonary arterial wedge pressure possible without sacrificing cardiac output or causing hypotension (see following discussion). β-Adrenergic agonists such as terbutaline have been shown to increase alveolar clearance of lung water, perhaps through the action of a sodium-potassium channel pump. Maintaining normal albumin levels and a hematocrit concentration above 30 maintains the filtration of lung liquid toward the capillaries.

High-altitude pulmonary edema (HAPE) occurs when susceptible individuals develop noncardiogenic edema after rapid ascent to altitudes above 3000 m. HAPE in children may be variable. Oxygen therapy and prompt descent are the cornerstones of therapy for this illness.

CONGENITAL PULMONARY LYMPHANGIECTASIA

Congenital pulmonary lymphangiectasia consists of dilated subpleural and interlobular lymphatic channels, often as part of a generalized lymphangiectasis (in association with obstructive cardiovascular lesions—especially total anomalous pulmonary venous return) or as an isolated idiopathic lesion. Pathologically, the lung appears firm, bulky, and noncompressible, with prominent cystic lymphatics visible beneath the pleura. On cut section, dilated lymphatics are present near the hilum, along interlobular septa, around bronchovascular bundles, and beneath the pleura. Histologically, dilated lymphatics have a thin endothelial cell lining overlying a delicate network of elastin and collagen.

Clinical Findings

Congenital pulmonary lymphangiectasia is a rare, usually fatal, disease that generally presents as acute, severe, or persistent respiratory distress at birth. There are reports of children developing symptoms in the first few months of life and others report diagnosis later in childhood. Chylothorax has been reported. Chest radiographic findings include a ground-glass appearance, prominent interstitial markings suggesting lymphatic distention, diffuse hyperlucency of the pulmonary parenchyma, and hyperinflation with depression of the diaphragm.

Congenital pulmonary lymphangiectasia may be associated with Noonan syndrome, asplenia, total anomalous pulmonary venous return, septal defects, atrioventricular canal, hypoplastic left heart, aortic arch malformations, and renal malformations. Patients with generalized lymphangiectasia have less severe pulmonary disease.

Prognosis

The outcomes for children with congenital pulmonary lymphangiectasia are improving due to improvements in perinatal respiratory support and care. Most deaths occur within weeks after birth and thereafter respiratory symptoms improve after the first year of life suggesting that maximal medical treatment remains warranted. In those with the most severe disease, rapid diagnosis is essential in order to expedite the option of lung transplantation.

SCOLIOSIS

Scoliosis is defined as lateral curvature of the spine and is categorized as idiopathic, congenital, or neuromuscular. No pulmonary impairment is typically seen with a Cobb angle showing thoracic curvature of less than 35 degrees. Most cases of idiopathic scoliosis occur in adolescent girls and are corrected before significant pulmonary impairment occurs. Congenital scoliosis of severe degree or with other major abnormalities carries a more guarded prognosis. Patients with progressive neuromuscular disease, such as Duchenne muscular dystrophy, can be at risk for respiratory failure due to severe scoliosis and restrictive lung disease. Severe scoliosis can also lead to impaired lung function and, if uncorrected, possible death from cor pulmonale. (See also Chapter 26.) Small studies indicate that surgical correction of neuromuscular scoliosis should lead to improved quality of life, although pulmonary function may not improve.

PECTUS CARINATUM

Pectus carinatum is a protrusion of the upper or lower (more common) portion of the sternum, more commonly seen in males. Impairment of cardiopulmonary function due to pectus carinatum is debated. The decision to repair this deformity is often based on cosmetic concerns. Patients with reduced endurance or dyspnea with mild exercise experienced marked improvement within 6 months following repair, suggesting possible physiologic indications. Pectus carinatum may be associated with systemic diseases such as the mucopolysaccharidoses and congenital heart disease.

PECTUS EXCAVATUM

Pectus excavatum is anterior depression of the chest wall that may be symmetrical or asymmetrical with respect to the midline. The effect of pectus excavatum on cardiopulmonary function is controversial. While subjective exertional dyspnea can be reported and may improve with repair, objective cardiopulmonary function may not change postoperatively. Therefore, the decision to repair the deformity may be based on cosmetic or physiologic considerations. Timing of repair is critical and based on growth plate maturation. Pectus excavatum may be associated with congenital heart disease, PCD, and neuromuscular disorders.

Neuromuscular disorders are discussed in detail in Chapter 25. Weakness of the diaphragm, intercostal muscles, and pharyngeal muscles leads to chronic or recurrent pneumonia secondary to weak cough and poor mucus clearance, aspiration and infection, persistent atelectasis, hypoventilation, and respiratory failure in severe cases. Scoliosis, which frequently accompanies neuromuscular disorders, may further compromise respiratory function. Children born with significant neuromuscular weakness may present with signs and symptoms of respiratory distress or failure early in life. The time to presentation for children with progressive or acquired neuromuscular disease depends on the underlying neuromuscular defect. Typical examination findings in children at increased risk for pulmonary disease are a weak cough, decreased air exchange, crackles, and dullness to percussion. The child also may have symptoms of sleep-related hypoventilation or OSA. Positional changes in chest movement and paradoxical thoracoabdominal movement during quiet breathing are indications of respiratory insufficiency. Signs of cor pulmonale may be evident in advanced cases. Chest radiographs generally show small lung volumes. Other radiographic findings include abnormal rib orientation and generalized osteopenia of disuse. If chronic aspiration is present, increased interstitial infiltrates and areas of atelectasis or consolidation may be present. Arterial blood gases demonstrate hypoxemia in the early stages and compensated respiratory acidosis in the late stages. Typical pulmonary function abnormalities include decreased vital capacity, decreased inspiratory and/or expiratory pressure, and decreased peak cough flow.

Treatment & Prognosis

Treatment is supportive and includes vigorous airway clearance with a focus on assisted cough maneuvers, noninvasive ventilation, and antibiotics with infection. Supplemental oxygen may correct hypoxemia but does not correct the mechanical defect leading to hypoxemia. Depending on the diagnosis, routine PSG may be indicated to identify hypoventilation before it becomes clinically apparent. Consideration of bilevel positive airway pressure and mechanical airway clearance support, like mechanical in-exsufflation, should be introduced before respiratory failure is present. Due to risk of malignant hyperthermia and difficulty extubating, expert consultation prior to any anesthesia is required.

Many neuromuscular conditions progress to respiratory failure and death. The decision to intubate and ventilate is a difficult one; it should be made only when there is real hope that deterioration, though acute, is potentially reversible or when chronic ventilation is desired. Chronic mechanical ventilation using either noninvasive or invasive techniques is being used more frequently in patients with chronic respiratory insufficiency. New therapies in spinal muscular atrophy, including gene replacement and antisense oligonucleotide, are changing the landscape of this disease.

The parietal pleura covers the inner surface of the chest wall. The visceral pleura covers the outer surface of the lungs. Disease processes can lead to accumulation of air or fluid or both in the pleural space. Pleural effusions are classified as transudates or exudates. Transudates occur when there is imbalance between hydrostatic and oncotic pressure, so that fluid filtration exceeds reabsorption (eg, congestive heart failure). Exudates form because of inflammation of the pleural surface leading to increased capillary permeability (eg, parapneumonic effusions). Other pleural effusions include chylothorax and hemothorax.

Thoracentesis is helpful in characterizing the fluid and providing definitive diagnosis. Recovered fluid is considered an exudate when Light’s criteria are present (pleural fluid–serum protein ratio > 0.5, a pleural fluid–serum LDH ratio > 0.6, or a pleural fluid LDH level greater than two-thirds the upper limit for normal serum LDH). Important additional studies on pleural fluid include cell count; pH and glucose; Gram stain, acid-fast and fungal stains; aerobic and anaerobic cultures; and counterimmunoelectrophoresis for specific organisms. Cytologic examination of pleural fluid should be performed to rule out leukemia or other neoplasm.

HEMOTHORAX

Accumulation of blood in the pleural space can be caused by surgical or accidental trauma, coagulation defects, and pleural or pulmonary tumors. A hemothorax is defined as a parapneumonic effusion when the hematocrit of the fluid is more than 50% of the peripheral blood. Hemopneumothorax may be caused by trauma. Symptoms are related to blood loss and compression of underlying lung parenchyma. There is some risk of secondary infection, resulting in empyema.

Treatment

Drainage of a hemothorax is required when significant compromise of pulmonary function is present, as with hemopneumothorax. In uncomplicated cases, observation is indicated because blood is readily absorbed spontaneously from the pleural space.

VATS has been used successfully in the management of hemothorax. Chest CT scan is helpful to select patients who may require surgery, as identification of blood and the volume of blood may be more predictive by this method than by chest radiograph.

CHYLOTHORAX

Accumulation of chyle, fluid of intestinal origin containing fat digestion products (mostly lipids), in the pleural space usually results from accidental or surgical trauma to the thoracic duct. The most common cause of a pleural effusion in the first few days of life is a chylothorax. In a newborn, chylothorax can be due to congenital abnormalities of the lymph vessels or secondary to birth trauma. Abnormalities of lymph vessels are seen in several congenital syndromes such as Down syndrome and Noonan syndrome. In an older child, a chylothorax can be due to laceration or obstruction of the thoracic duct due to trauma or any surgery involving the chest wall (cardiac surgery, scoliosis repair, etc); obstruction of the vessels due to a benign or malignant mass or lymphadenopathy; a granulomatous infection such as tuberculosis; or increased venous pressure due to obstruction or left ventricular failure. Symptoms of chylothorax are related to the amount of fluid accumulation and the degree of compromise of underlying pulmonary parenchyma. Thoracentesis reveals typical milky fluid (unless the patient has been fasting) containing chiefly T lymphocytes.

Treatment

Treatment should be conservative because many chylothoraces resolve spontaneously. Oral feedings with medium-chain triglycerides reduce lymphatic flow through the thoracic duct. Somatostatin or the long-acting somatostatin analogue, octreotide, are viable therapeutic options. Drainage of chylous effusions should be performed only for respiratory compromised because the fluid often rapidly reaccumulates. Repeated or continuous drainage may lead to protein malnutrition and T-cell depletion, rendering the patient relatively immunocompromised. If reaccumulation of fluid persists, surgical ligation of the thoracic duct or sclerosis of the pleural space can be attempted, although the results may be less than satisfactory.

PNEUMOTHORAX & RELATED AIR LEAK SYNDROMES

Pneumothorax can occur spontaneously in newborns and in older children or, more commonly, as a result of birth trauma, positive pressure ventilation, underlying obstructive or restrictive lung disease, or rupture of a congenital or acquired lung cyst. Pneumothorax can also occur as an acute complication of tracheostomy. Air usually dissects from the alveolar spaces into the interstitial spaces of the lung. Migration to the visceral pleura ultimately leads to rupture into the pleural space. Associated conditions include pneumomediastinum, pneumopericardium, pneumoperitoneum, and subcutaneous emphysema. These conditions are more commonly associated with dissection of air into the interstitial spaces of the lung with retrograde dissection along the bronchovascular bundles toward the hilum.

Clinical Findings

A. Symptoms and Signs

The clinical spectrum can vary from asymptomatic to severe respiratory distress. Associated symptoms include cyanosis, chest pain, and dyspnea. Physical examination may reveal decreased breath sounds and hyperresonance to percussion on the affected side with tracheal deviation. When pneumothorax is under tension, cardiac function may be compromised, resulting in hypotension or narrowing of the pulse pressure. Pneumopericardium is a life-threatening condition that presents with muffled heart tones and shock. Pneumomediastinum rarely causes complications other than chest pain.

B. Laboratory Findings and Imaging Studies

Chest radiographs demonstrate the presence of free air in the pleural space. When the pneumothorax is large and under tension, compressive atelectasis of the underlying lung and shift of the mediastinum to the contralateral side may be observed. Cross-table lateral and lateral decubitus radiographs can aid in the diagnosis of free air. Pneumopericardium is identified by the presence of air entirely surrounding the heart, whereas in patients with pneumomediastinum, the heart and mediastinal structures may be outlined with air, but the air does not involve the diaphragmatic cardiac border. Chest CT may identify subtle pleural disease (eg, blebs) in recurrent pneumothoraces.

Differential Diagnosis

Acute deterioration of a patient on a ventilator can be caused by tension pneumothorax, obstruction or dislodgment of the endotracheal tube, or ventilator failure. Radiographically, pneumothorax must be distinguished from diaphragmatic hernia, lung cysts, congenital lobar emphysema, and CPAM.

Treatment

Small (< 15%) or asymptomatic pneumothoraces usually do not require treatment and can be managed with close observation. Larger or symptomatic pneumothoraces require drainage, although inhalation of 100% oxygen to wash out blood nitrogen can be tried. Needle aspiration should be used to relieve tension acutely, followed by chest tube or pigtail catheter placement. Pneumopericardium requires immediate identification, and if clinically symptomatic, needle aspiration to prevent death, followed by pericardial tube placement.

Prognosis

In older patients with spontaneous pneumothorax, recurrences are common; sclerosing and surgical procedures are often required.

MEDIASTINAL MASSES

Children with mediastinal masses may present because of symptoms produced by pressure on the esophagus, airways, nerves, or vessels within the mediastinum, or the masses may be discovered incidentally on chest radiograph. Once the mass is identified, localization to one of four mediastinal compartments aids in the differential diagnosis. The superior mediastinum is the area above the pericardium that is bordered inferiorly by an imaginary line from the manubrium to the fourth thoracic vertebra. The anterior mediastinum is bordered by the sternum anteriorly and the pericardium posteriorly, and the posterior mediastinum is defined by the pericardium and diaphragm anteriorly and the lower eight thoracic vertebrae posteriorly. The middle mediastinum is surrounded by these three compartments.

Clinical Findings

A. Symptoms and Signs

Respiratory symptoms, when present, are due to pressure on an airway (cough or wheezing) or an infection (unresolving pneumonia in one area of lung). Hemoptysis can also occur but is an unusual presenting symptom. Dysphagia may be due to compression of the esophagus. Pressure on the recurrent laryngeal nerve can cause vocal cord paralysis and hoarse voice. Superior vena caval syndrome presents with dilation of neck vessels and other signs and symptoms of venous obstruction; superior mediastinal syndrome presents similarly but includes tracheal compression.

B. Laboratory Findings and Imaging Studies

The mass is initially defined by frontal and lateral chest radiographs together with chest CT scans or MRI. A barium esophagram may help define the extent of a mass. Other studies that may be required include angiography (to define the blood supply to large tumors), electrocardiography, echocardiography, ultrasound of the chest, fungal and mycobacterial skin tests, and urinary catecholamine assays. MRI or myelography may be necessary in children suspected of having a neurogenic tumor in the posterior mediastinum. Mediastinal masses, particularly anterior masses, can cause life-threatening airway compromise in the supine position and during sedation even in patients with mild symptoms; thus, any sedation or anesthesia should be avoided if possible and performed cautiously.

Differential Diagnosis

The differential diagnosis of mediastinal masses is determined by their location. Superior mediastinal masses include cystic hygromas, vascular or neurogenic tumors, thymic masses, teratomas, intrathoracic thyroid tissue, mediastinal abscess, and esophageal lesions. Anterior mediastinal masses include thymic tissue (thymomas, hyperplasia, and cysts), intrathoracic thyroid, teratomas, vascular tumors, reactive lymphadenopathy, leukemia, and lymphoma. Middle mediastinum masses include lymphomas, hypertrophic lymph nodes, granulomas, bronchogenic or enteric cysts, metastases, and pericardial cysts. Abnormalities of the great vessels and aortic aneurysms may also present as masses in this compartment. Posterior mediastinal masses include neurogenic tumors, enterogenous cysts, thoracic meningoceles, and aortic aneurysms.

In some series, more than 50% of mediastinal tumors occur in the posterior mediastinum and are mainly neurogenic tumors or enterogenous cysts. Most neurogenic tumors in children younger than 4 years are malignant (neuroblastoma or neuroganglioblastoma), whereas a benign ganglioneuroma is the most common histologic type in older children. In the middle and anterior mediastinum, lymphoma and leukemia are the primary concern. Definitive diagnosis in most instances relies on surgical excision or biopsy for histologic examination.

Treatment & Prognosis

The appropriate therapy and the response to therapy depend on the cause of the mediastinal mass.

Sleep apnea is recognized as a major public health problem in adults, due to its associated impact on health and the risks of excessive daytime sleepiness, impairment while driving, and poor work performance. Pediatric sleep-related breathing disorders are less commonly recognized because the risk factors, presentations, management, and outcomes differ from those in adults, although the adverse impact on health is similar in scope and perhaps severity. SDB in children has been associated with problems in a multitude of realms, including social, behavioral, and neurocognitive. It has been shown to significantly impact quality of life and has been associated with growth impairment and cardiovascular complications. Recent studies also indicate that sleep-disordered breathing (SDB) is associated with systemic inflammation.

SDB is any abnormal respiratory pattern during sleep, which may include noisy breathing, mouth breathing, and/or pauses in breathing that may be obstructive, central, or mixed in etiology. SDB encompasses a spectrum of obstructive disorders from primary snoring to OSA, but also includes periodic breathing, central sleep apnea, hypoventilation syndromes, etc. SDB is a presumptive clinical diagnosis where PSG is necessary to more specifically characterize the disorder.

Clinical Findings

A. Symptoms and Signs

Obstructive sleep apnea (OSA) occurs in normal children with an incidence of about 2%, increasing in children with medical conditions such as craniofacial abnormalities or neuromuscular diseases, or use of medications, such as hypnotics, sedatives, or anticonvulsants. OSA should be suspected whenever a child presents with symptoms of loud or habitual snoring (snoring 3 or more nights per week), witnessed apnea, labored breathing, mouth breathing, or frequent nighttime arousals, especially in the setting of failure to thrive or obesity, nocturnal oxygen desaturations, life-threatening events, craniofacial abnormalities, poor school performance, or behavioral problems such as hyperactivity. In children, airway obstruction is often associated with nasal congestion, atopy, and adenotonsillar hypertrophy, where tonsillar hypertrophy is most common between the ages of 2 and 7 years. Obesity is widely recognized as an etiologic component in adult OSA and is increasingly cited in pediatric OSA.

B. Diagnostic Studies: Polysomnography & Airway Evaluation

In 2012, the AAP updated their clinical practice guideline for the diagnosis and management of uncomplicated childhood OSA syndrome. The guideline emphasizes that pediatricians should screen all children for snoring. If the child exhibits additional signs and symptoms of SDB, referral for a sleep study is recommended, but referral to an otolaryngologist or sleep specialist is also an option. The American Academy of Sleep Medicine (AASM) has similar recommendations.

A patient’s history and clinical examination cannot predict the presence or severity of OSA. Similarly, an overnight oximetry study is a poor screening test for OSA, as obstructive respiratory events can occur without oxygen desaturations. Therefore, the gold standard for diagnosis of OSA is a PSG, commonly called a “sleep study.” This test measures sleep state with electroencephalogram leads and electromyography, oronasal airflow, chest and abdominal effort, heart rate and rhythm, gas exchange (O₂ and CO₂), and leg movements, along with body position, vibrations representing snoring, and audiovisual recording. PSG is utilized not only for characterizing SDB but also for diagnosing periodic limb movements. Sleep apnea is defined as cessation of breathing and can be classified as obstructive (airflow stops despite persistence of respiratory effort) or central (the lack of effort to breathe). A hypopnea is counted when airflow and respiratory effort decrease for at least two respiratory cycles with an associated oxygen desaturation or arousal. The criteria for diagnosing OSA differ between children and adults, and normative values for children are still being established. The AASM states that for children, the occurrence of more than one apnea-plus-hypopnea per hour of sleep (the apnea-hypopnea index, or AHI) is abnormal. However, the AASM has qualified its recommendation, stating that the criteria may be modified once more comprehensive data become available. One study of children aged 6–11 years found that an AHI of between one and five events per hour (mild OSA) was associated with daytime sleepiness and learning problems when associated with 3% oxygen desaturation, whereas an AHI of five events per hour or more (moderate to severe OSA) was associated with clinical symptoms even in the absence of desaturation. Notably, many studies have shown little correlation between the severity of OSA by PSG and morbidity. Furthermore, even primary snoring, which is habitual snoring without gas exchange abnormalities or arousals, has been associated with neurobehavioral consequences.

A PSG is generally recommended for children with suspected sleep apnea if they have any of the following comorbid conditions: obesity, Down syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses. PSG also is recommended for children without the above comorbidities if the need for surgery is uncertain, or if there is discordance between tonsillar size on physical examination and the reported severity of symptoms, no adenotonsillar hypertrophy or nasal obstruction, but significant symptoms of SDB for example. Other conditions, especially a periodic limb movement disorder, may mimic the daytime symptoms of SDB.

If a PSG indicates OSA in a child without tonsillar hypertrophy, a complete evaluation of the upper airway by awake flexible laryngoscopy should be performed to look for other possible sites of obstruction, including the nose (turbinate hypertrophy), nasopharynx (adenoid), hypopharynx (base of tongue or lingual tonsils), and larynx (laryngomalacia). The adenoid can also be assessed with a lateral neck x-ray. Alternative methods to evaluate a child for anatomical sites of obstruction include sedated cine MRI of the upper airway or drug-induced sleep endoscopy (DISE).

Clinical Evaluation & Management

Most pediatric otolaryngologists perform adenotonsillectomy (AT) in healthy patients with obstructive SDB without obtaining a PSG. AT without PSG may be considered in a healthy child if the following are present:

1. Nighttime symptoms: habitual snoring along with gasping, pauses, or labored breathing. Other symptoms that may be related to SDB include night terrors, sleep walking, secondary enuresis, or morning headaches.

2. Daytime symptoms: unrefreshed sleep, attention deficit, hyperactivity, emotional lability, temperamental behavior, poor weight gain, and daytime fatigue. Other signs include daytime mouth breathing or dysphagia.

3. Enlarged tonsils.

If the three findings cannot be confirmed, but the child has other indications for an AT—that is, recurrent tonsillitis or markedly enlarged (4+) tonsils with dysphagia—referral to a pediatric otolaryngologist to consider surgery is warranted. See Chapter 18 for a thorough discussion of AT.

Figure 19–5 is an algorithm for management of SDB complaints in an otherwise healthy child. The pathway relies on clinical symptoms and tonsil size. The most commonly used grading scale for tonsil size ranges from 0 to 4. With grade 1 the tonsils are small and contained within the tonsillar fossa; in grade 4 the tonsils are so large they may touch (“kissing”); grade 0 describes prior tonsillectomy. As mentioned, tonsil size alone does not predict the presence of significant SDB, as children without significant tonsil hypertrophy may still have OSA due to factors such as low muscle tone, atopy, etc. Clinical suspicion of SDB should be heightened if a child has enlarged tonsils, especially if the parents cannot provide a reliable history. Although the pathway states that an asymptomatic child with markedly enlarged tonsils (4+) should undergo PSG, a period of observation or trial of conservative management is reasonable. If the child has no clinical symptoms and the tonsils are only moderately enlarged (3+), observation is appropriate. Educating the parents about the risks of SDB and what to look for is paramount.

A landmark randomized prospective study on AT outcomes (CHAT Study) demonstrated overall success at 79%. Success was defined as AHI reduced to less than 2 and obstructive apnea index to less than one event an hour. Obesity, black ethnicity, and an AHI more than 4.7 events an hour were associated with lower cure rates. Interestingly, 47% of the children in the watchful waiting group had spontaneous resolution of their OSA at 7 months. Children who had mild OSA or normal weight were more likely to improve spontaneously.

As for postoperative PSG, the AASM and AAP agree that a child with mild OSA (AHI fewer than five events an hour) does not require a follow-up study. However, those with persistent symptoms, more severe OSA, obesity, or other comorbidities should routinely have a postoperative study. When OSA persists or AT is contraindicated/refused/delayed for whatever reason, treatment with continuous or bilevel positive airway pressure (CPAP or BiPAP) may be considered.

Regardless of the underlying etiology of SDB, maintaining a healthy weight, addressing abnormal dentition (with the use of orthodontics, such as oral appliances or rapid maxillary expanders) and optimizing airway health (by treating nasal obstruction, atopy, and asthma with topical intranasal steroids and leukotriene modifiers, for example) are cornerstones of OSA management.

Pediatric sleep-related breathing disorders of central etiology, including periodic breathing and central sleep apnea, are less well understood. Central apneas are common in infants and children, particularly at increased elevation. These are pauses in breathing without concomitant effort and may occur in a pattern of alternating apnea and tachypnea known as periodic breathing. Clinical significance is uncertain, as healthy children have been shown to have central apneas lasting 25 seconds without clear consequences. These central respiratory events may be relevant if they occur frequently or are associated with gas exchange abnormalities or sleep fragmentation, and should then prompt a thorough evaluation by a pediatric sleep specialist. Though no intervention is needed in most cases of periodic breathing and central sleep apnea, supplemental oxygen may be used to reduce oxygen desaturation and stabilize the respiratory pattern.

In 2016, the AAP suggested renaming apparent life-threatening events (ALTE) to brief resolved unexplained events (BRUE), just as ALTE previously replaced “near-miss sudden infant death syndrome” (SIDS). The BRUE nomenclature serves to clarify clinical care and research, while also providing a framework for evaluation of lower-versus higher-risk infants following a BRUE. BRUEs are defined in infants younger than 1 year who are observed to have apnea or irregular breathing, cyanosis or pallor (not redness), marked change in muscle tone (either hypotonia/limpness or hypertonia), or decreased responsiveness that lasts less than 1 minute (more often < 20–30 seconds) and returns to baseline with subsequent reassuring history and physical examination by a clinician. This definition highlights that the event remains unexplained, whereas the ALTE label overlaps with events such as fever, upper airway congestion, or labored respirations attributable to acute viral illness, or gagging/choking with gastroesophageal reflux, as examples.

Once a clinician has made the BRUE diagnosis, the infant is determined to be either low or high risk, which will determine what, if any, evaluation is needed. Infants with a BRUE are considered high risk if they are younger than 60 days, were born less than 32 weeks’ gestation, received CPR at the time of the event, or have had a prior BRUE.

Immaturity likely plays a major role in the pathogenesis of BRUEs. Classic studies on the nervous system, reflexes, or responses to apnea or gastroesophageal reflux during sleep in infants and immature animals show profound cardiovascular changes during stimulation of the vagus nerve, whereas adults are not affected.

The relationship between ALTE/BRUE and future risk of SIDS or sudden unexpected infant death (SUID) is not clear, as ALTE/BRUE infants tend to be younger. See the following SUID/SIDS section for more detail.

Clinical Findings & Differential Diagnosis

A. Symptoms and Signs

.A careful history is the most helpful part of the evaluation. A history of several days of poor feeding, temperature instability, or respiratory or gastrointestinal symptoms suggests an infectious process. Reports of “struggling to breathe” or “trying to breathe” imply airway obstruction. Episodes following crying may be related to breath-holding spells. Association of the episode with feeding implies dis-coordinated swallowing with or without aspiration, gastroesophageal reflux, or delayed gastric emptying, or may imply an airway abnormality. Episodes occurring while awake are associated with very different diagnoses than episodes occurring during sleep. Association of episodes with sleep may suggest seizure, gastroesophageal reflux, apnea of infancy, or SDB. It is helpful to role-play the episode with the family and then use the event characteristic (such as cyanosis, hypotonia, unresponsiveness, etc) to describe the event, as opposed to the vaguer term “ALTE.” Details regarding the measures taken to resuscitate the infant and the infant’s recovery from the episode may be useful in determining severity. Table 19–8 classifies disorders that may present as higher-risk BRUEs.

The physical examination provides further direction in pursuing the diagnosis. Fever or hypothermia suggests infection. An altered state of consciousness implies a postictal state or drug overdose, or central nervous system anomaly or infection. Respiratory distress implies cardiac or pulmonary lesions.

Apneic episodes have been linked to child abuse in several ways. Head injury following nonaccidental trauma may be first brought to medical attention because of apnea. Other signs of abuse are usually immediately apparent in such cases. Drug overdose, either accidental or intentional, may also present with apnea. Several studies document that apneic episodes may be falsely reported by parents who are seeking attention (ie, Munchausen syndrome by proxy, now referred to as medical child abuse). Parents may physically interfere with a child’s respiratory efforts, in which case pinch marks on the nares are sometimes found.

B. Laboratory Findings

Patients with low-risk BRUEs may not need inpatient observation or further testing. One may consider pertussis testing, electrocardiogram, brief pulse oximetry, and/or serial observations based on history, examination, or suspicion, but other blood work, lumbar puncture, imaging, acid-suppression therapy, hospitalization, etc are generally discouraged as they provoke unwarranted worry and stress in both patients and caregivers.

Those at high risk, however, should undergo more thorough evaluation for potential underlying etiologies, as referenced in Table 19–8, where clinical suspicion prioritizes the appropriate workup. In these cases, patients may be hospitalized for observation in order to reduce stress on the family and allow prompt completion of the evaluation. Diagnostic testing should be based primarily on the history and physical examination. Laboratory evaluation might include a complete blood count, blood culture with urinalysis, and urine culture for evidence of infection, especially in the face of fever, hypothermia, or an abnormal physical examination. Serum electrolytes may reveal electrolyte disturbances from metabolic disorders, dehydration, or ingestions. An elevation in serum bicarbonate indicates chronic hypoventilation, whereas decreases indicate acute acidosis, perhaps due to hypoxia during the episode. Chronic acidosis suggests an inherited metabolic disorder. Arterial blood gas studies provide an initial assessment of oxygenation and acid-base status. Low PaO_2, elevated PaCO_2, or both indicate cardiorespiratory disease. A significant base deficit suggests that the episode was accompanied by hypoxia or circulatory impairment. Oxygen saturation measurements in the hospital assess oxygenation status during different activities and are more comprehensive than a single blood gas sample. Because apnea has been associated with respiratory infections, diagnostic studies for RSV and other viruses, Bordetella pertussis, and Chlamydophila pneumoniae may help with diagnosis. Apnea occurring with infection often precedes other physical findings.

C. Imaging Studies

The chest radiograph is examined for infiltrates indicating acute infection or chronic aspiration and for cardiac size as a clue to intrinsic cardiac disease. Electrocardiogram is helpful to rule out cardiac dysrhythmias, and echocardiogram may be indicated if there is suspicion of congenital heart disease based on history and physical examination. If the episode might have involved airway obstruction, the airway should be examined either directly by fiberoptic bronchoscopy or radiographically by CT. VFSS or FEES can be done to evaluate for dysphagia and aspiration, and UGI fluoroscopy series is a useful tool to rule out the possibility of anatomic abnormalities such as vascular ring and tracheoesophageal fistula. Gastroesophageal reflux is common in infants; however, it may be a marker of autonomic immaturity as opposed to a cause of the event. Infants with reflux and apnea can be given medical antireflux treatment. Infants with reflux and repeated episodes of apnea may benefit from evaluation by a multidisciplinary aerodigestive team.

D. Special Tests: Polysomnography and Other Studies

Depending on the discretion of the clinician, PSG can be useful in detecting abnormalities of cardiorespiratory function, sleep state, oxygen saturation, carbon dioxide retention, and seizure activity. Sleep studies can be used in conjunction with pH monitoring to determine the contribution of reflux to apnea. Esophageal pressure manometry can be useful to detect subtle changes in espiratory effort related to partial obstructive breathing (hypopnea). Due to their immature nervous system, infants are more likely to experience adverse events from sleep disordered breathing than adults.

Among the neurologic causes of BRUEs, seizure disorder has been found to be a cause of BRUE in a significant number of cases. Apnea as the sole manifestation of a seizure disorder is unusual but may occur. In cases of repeated episodes, 24-hour electroencephalographic monitoring may be helpful in detecting a seizure disorder.

Treatment

Therapy is directed at the underlying cause, if one is found. After blood cultures are taken, antibiotics should be given to infants who appear toxic. Seizure disorders are treated with anticonvulsants. Gastroesophageal reflux should be treated if symptomatic, though this may not prevent future episodes. Cardiovascular anomalies, such as vascular rings and pulmonary slings, require cardiovascular surgical evaluation considering the potential for severe morbidity and mortality.

For both low- and high-risk BRUEs caregivers should be provided with education to reduce modifiable risk factors and taught CPR. Home monitoring has been used in the past as treatment, but the efficacy of monitoring has not been demonstrated in controlled trials. After more than 30 years of home monitoring, the sudden infant death rate has not changed. Although monitors can detect central apnea or bradycardia, they do not predict which children will have future events or SUID. Apnea monitors are prone to frequent false alarms, and it must be noted that many parents cannot handle the stress associated with having a monitor in the home.

Supplemental oxygen has been used as therapy for BRUEs for several reasons. Oxygen reduces periodic breathing of infancy, an immature pattern of breathing that can cause some degree of oxygen desaturation. Second, infants have small chest capacities with increased chest wall compliance that reduces lung volume. Supplemental oxygen can increase the baseline saturation, reducing the severity of desaturation with short apneas. Respiratory stimulants such as caffeine and aminophylline have been used in specific cases of central apnea or periodic breathing.

Prevention

All infants younger than 1 year should be evaluated for the presence of modifiable SUID risk factors. Parents should be educated on how to avoid these risk factors, especially in infants at increased risk such as former preterm infants, children exposed to cigarette smoke environmentally or prior to birth, African American or Native American infants, and infants in poor socioeconomic areas. Recommendations from the AAP Task Force on SIDS include:

• Always place a baby on its back to sleep (this includes a baby with reflux).

• Infants should sleep in the parents’ room, close to the parents’ bed but on a separate surface designed for infants, ideally for the first year of life but at least for the first 6 months.

• Soft objects and loose bedding, including blankets, nonfitted sheets, stuffed animals, or wedge positioners, should be kept away from the infant’s sleep area to reduce the risk of SIDS, suffocation, entrapment, and strangulation.

  • Wearable blankets are preferred to blankets and other coverings to keep the infant warm while reducing the chance of head covering. There is no evidence to recommend swaddling as a strategy to reduce the risk of SIDS.

  • Avoid overheating, overwrapping, and covering the face and head.

• Breast-feeding is recommended.

• Consider offering a pacifier at naptime and bedtime.

• Avoid exposure to cigarette smoke during pregnancy and after birth.

• Car seats, swings, and baby slings should not be used for sleep as the infant’s head tends to fall forward or to the side, compromising the airway.

• Avoid the use of adult beds, bed rails, etc, which increase the risk of suffocation and entrapment.

  • There are no studies supporting the safety of bedside or in-bed sleepers, and therefore these products cannot be recommended.

• Health care professionals, hospital staff, and childcare providers should endorse and model infant safe sleep recommendations from birth.

• Pediatricians and other primary care providers should actively participate in the “Safe to Sleep” campaign, focusing on ways to reduce the risk of all sleep-related infant deaths, including SIDS, suffocation, and other unintentional deaths.

SUDDEN UNEXPECTED INFANT DEATH & SUDDEN INFANT DEATH SYNDROME

SIDS is defined as the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. The postmortem examination is an important feature of the definition because approximately 20% of cases of sudden death can be explained by autopsy findings. After the “Back to Sleep” campaign began in the United States in 1994, the incidence of SIDS declined from approximately 2 per 1000 to 0.5 per 1000 live births. However, the incidence of SIDS has leveled off since 1999.

SUID, defined as any sudden and unexpected infant death, whether explained (such as accidental suffocation or strangulation) or unexplained (such as SIDS) has gained favor as the preferred term to refer to infant deaths that were previously classified as SIDS. SIDS is neither a true diagnosis nor a syndrome, and labeling an infant death as SIDS tends to give parents a false sense that the cause of their child’s death is known and understood. SUID also includes deaths due to infection, ingestions, metabolic diseases, cardiac arrhythmias, and trauma. Recent evidence shows that the incidence of accidental suffocation and strangulation in bed is increasing due to unsafe sleep surfaces and environments.

Epidemiology & Pathogenesis

Epidemiologic and pathologic data constitute most of what is known about SUID. Like SIDS, SUID deaths peak between ages 2 and 4 months. Most deaths occur at night, while the infant and the caregiver are sleeping. In fact, the only unifying features of all cases are age and sleep. SUID is more common among ethnic and racial minorities and socioeconomically disadvantaged populations. Racial disparity in the prevalence of prone positioning and especially in bed-sharing may be contributing to the continued disparity in SUID rates between black and white infants. There is a 3:2 male predominance in most series. Other risk factors include preterm birth, low birth weight, recent infection, young maternal age, high maternal parity, maternal tobacco or drug use, and crowded living conditions. Most of these risk factors are associated with a two- to threefold increased incidence but are not specific enough to be useful in predicting which infants will die unexpectedly. Recent immunization is not a risk factor.

The most consistent pathologic findings in SUID deaths from unknown cause (previously classified as SIDS) are intrathoracic petechiae and mild inflammation and congestion of the respiratory tract. More subtle pathologic findings include brainstem gliosis, extramedullary hematopoiesis, and increases in periadrenal brown fat. These latter findings suggest that infants who succumb to SUID have had intermittent or chronic hypoxia before death.

In cases where a distinct cause cannot be identified, the mechanism or mechanisms of death in SUID are unknown. For example, it is unknown whether the initiating event at the time of death is cessation of breathing, cardiac arrhythmia, or asystole. Hypotheses have included upper airway obstruction, catecholamine excess, and increased fetal hemoglobin. However, maldevelopment or delayed maturation of the brainstem, which is responsible for arousal from sleep, remains the predominant theory. A history of mild symptoms of upper respiratory infection before death is not uncommon, and SUID victims are sometimes seen by physicians a day or so before death. The postmortem examination is essential and may help the family by excluding other possible causes of death. A death scene investigation is also important in determining the cause of sudden unexpected deaths in infancy.

Families must be supported following the death of an infant. The National SIDS Resource Center (http://www.sidscenter.org) provides information about psychosocial support groups and counseling for families of SIDS victims.

Prevention

Since 1990, SIDS rates have declined more than 60% worldwide. Population studies in New Zealand and Europe identified risk factors, which when changed had a significant effect on the incidence of SIDS. Since 1994 the AAP’s “Back to Sleep” campaign has promoted education about the risk of prone positioning.

QUALITY ASSESSMENT & OUTCOMES METRICS

Pediatric pulmonary medicine is constantly adjusting to improve the outcomes for children with respiratory illness. The foundation of the work in quality improvement is in the many clinical care guidelines that inform the care of patients and in the data that indicate the success of the care. For example, as mentioned (and referenced) earlier, the Cystic Fibrosis Foundation works with providers and centers of care to create and implement guidelines for the diagnosis and management of children with CF. This foundation also maintains a registry of children with CF and reports on outcomes including lung function, body mass index, and mortality data. The ChILD foundation mentioned earlier has also created guidelines for diagnosis and management and follows patient outcomes including those mentioned above. The National Heart, Lung, and Blood Institute has updated the asthma guidelines three times. International and United States based organizations have studied adherence to those guidelines. The Centers for Disease Control and Prevention in the United States reports asthma outcomes including utilization, mortality, and cost of care. AAP, as mentioned earlier, has published guidelines for SIDS and SUID prevention. There are ongoing studies of the impact of those guidelines and the data demonstrates clearly that these guidelines are saving lives. Finally, respiratory disease requires a multidisciplinary team to care for patients in and out of the hospital. The American Academy of Respiratory Care publishes guidelines on oxygen use, aerosolized device use, and ventilation (acute and chronic) for pediatric patients.