Pediatric Otorhinolaryngology: Diagnosis and Treatment, 1st Ed.

14

Inflammatory Airway Disease

Kara K. Prickett and Steven E. Sobol

Respiratory infections are the leading cause of death among children less than 5 years of age, with significant morbidity and mortality attributed to acute inflammatory obstruction of the airway.1 The anatomy of the pediatric airway leaves children particularly susceptible to obstructive respiratory compromise. Children have proportionately larger heads, larger tongues, and less cervical support than adults, leading to relative narrowing of the upper airway in the supine position. The pediatric airway is narrowest in the subglottis, where the outer diameter is fixed by the cricoid and loosely adherent mucosa allows for significant changes in inner diameter in the setting of inflammatory infiltrates. Turbulent flow of air through the narrowed subglottis is perceived as stridor. Children presenting with acute onset of stridor or rapidly progressing symptoms must be promptly managed to avoid complications.

Croup

The term “croup” was introduced into the medical lexicon in the late 1700s as a derivation of the Anglo-Saxon and Scottish terms for a loud or harsh cry, and was used to describe illness caused by diphtheria. Today, croup describes laryngotracheobronchitis, a virally mediated condition characterized by inflammatory obstruction of the glottic and sub-glottic airways.

Epidemiology

Croup has been implicated in up to 90% of cases of infectious upper airway obstruction. Children under 6 years of age are affected most commonly, with peak incidence between 6 and 36 months. Males are affected 1.5 times as often as females.2 The incidence of croup peaks in the autumn and mid-winter, corresponding with epidemiology of common viral illnesses in children.

Pathophysiology

Most cases of croup are caused by the human parainfluenza viruses. The inflammatory response to infection, rather than direct viral damage to the epithelium, is likely responsible for most clinical symptoms. Viral titers have been found to be waning at the time of symptom onset.1 Increased capillary permeability contributes to edema and the formation of thick secretions. Subglottic narrowing leads to the characteristic inspiratory stridor.

Host factors that may contribute to more severe infection are targets of current investigation. Defective suppression of the immunologic response to viral antigens and infection with atypical pathogens has been linked to prolonged or severe symptoms. Respiratory syncytial virus, Mycoplasma pneumoniae, herpes simplex virus, paramyxovirus, adenovirus, and varicella have all been reported as etiologic agents. More recently, human metapneumovirus and coronavirus have also been linked to croup.1

Clinical Presentation

After 1 or 2 days of viral prodrome, hoarseness, inspiratory stridor, and a seal-like, barking cough develop in most patients. Symptoms worsen at night or with agitation and gradually resolve over 3 to7 days. Less than 5% of children with croup require hospitalization, and of those admitted, only 1 to 3% require intubation.3 Rapid onset of symptoms (<12 hours) or signs of extreme toxicity should alert the clinician to both the potential need for rapid airway management and the consideration of other possible diagnoses. The differential diagnosis of croup is shown in Table 14.1.

Spasmodic croup is a well-described, but poorly-understood, clinical syndrome of barking cough, stridor, and respiratory distress, which occurs almost exclusively at night. Patients lack the viral prodrome associated with classic croup. Symptoms are typically self-limited, and may resolve before arrival in the emergency department. Children with spasmodic croup are often older than the classic young child with viral laryngotracheobronchitis. Recurrence over several subsequent nights is common.4 The etiology of spasmodic croup is unknown, but may be related to atopy.5

Evaluation and Initial Management

The diagnosis of croup can usually be made clinically. When the initial diagnosis is made by an experienced practitioner using clinical criteria, only 2% of cases are eventually given an alternate diagnosis. Several scoring systems have been developed to stratify patients by disease severity. The Westley Croup Scoring System is widely used in treatment trials, but has not been validated as an effective tool for clinical decision making.5

In the stable child, birth history, history of earlier intubations, and recent exposures should be obtained. The absence of a cough should lead the clinician to consider alternative diagnoses. Children under 6 months of age should be examined for cutaneous hemangiomas, as symptoms of subglottic hemangioma may mimic those of croup.

Radiographic findings of the characteristic “steeple sign” or dilation of the hypopharynx are 92% specific for croup (Fig. 14.1).6 Because the sensitivity of neck radiographs ranges from 50 to 93%, a normal radiograph does not rule out the diagnosis.7 Laboratory studies typically yield non-specific signs of inflammation or viral infection. Flexible fiberoptic laryngoscopy may rule out other glottic or supraglottic pathology, but provides limited examination of the subglottis.

Table 14.1 Differential Diagnosis of Croup

Congenital

Laryngomalacia

Vocal fold paralysis

Laryngeal web

Subglottic stenosis

Subglottic hemangioma

Tracheomalacia

Vascular

Innominate artery compression

Double aortic arch

Aberrant subclavian artery

Pulmonary artery sling

Infectious/Inflammatory

Recurrent respiratory papillomatosis

Epiglottitis

Peritonsillar abscess

Deep neck space infection

Diphtheria

Bacterial tracheitis

Mycobacteria

Laryngeal candidiasis

Angioedema

Wegener granulomatosis

Sarcoidosis

Extraesophageal reflux

Traumatic/Toxic

Acquired subglottic stenosis

Inhalational injury

Foreign body

Neoplastic

Benign or malignant lesions

Adapted from: Sobol SE, Zapata S. Epiglottitis and croup. Otolaryngol Clin North Am 2008;41(3):551–566.

Definitive Therapy

Systemic corticosteroids are the mainstay of treatment for croup.8 Oral or intramuscular dosing is preferred due to ease of administration and low cost, but recent research has shown nebulized budesonide to be equally efficacious.8,9The most common regimens consist of single doses of prednisolone 1 mg/kg or dexamethasone 0.6 mg/kg. No data are available on the utility of multiple-dose regimens.

Helium–oxygen mixtures (heliox) can decrease work of breathing in patients with narrowed airways, as the lowered density of such inhaled mixtures can maintain or improve flow of air even with reduced airway caliber. Promising results have been obtained in several small, uncontrolled reviews, but randomized trials have thus far shown only statistically insignificant trends toward improvement in children treated with heliox.10

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Figure 14.1 An anteroposterior radiograph typical of a patient with croup. Edema in the subglottis produces the “steeple” appearance. Dilation of the hypopharynx due to forceful inspiration against an obstructed subglottis is best appreciated on a lateral film.

The effectiveness of inhaled racemic epinephrine has been proven in several well-designed trials.11 Alpha-adrenergic effects decrease capillary permeability, while beta-2 effects contribute to smooth muscle relaxation.12 Overnight observation after treatment with racemic epinephrine, while once standard of practice, is no longer considered imperative. Recent studies have shown that it is safe to discharge patients after 2 to 4 hours of observation if clinical signs of croup do not return.13

Hospitalization is indicated for severe symptoms, failure to improve, and poor access to follow-up care.4 Treatment is largely supportive, as there is no evidence to support the use of antibiotics, antitussives, or decongestants. Similarly, recent studies have failed to show any benefit for children treated with humidified air or mist therapy.14 Current evidence-based recommendations for pharmacotherapy in croup are summarized in Table 14.2. The need for intubation has decreased markedly in the era of widely available corticosteroids, and tracheotomy is rarely performed. When intubation is necessary, the smallest effective endotracheal tube should be selected to minimize trauma to the already inflamed airway.

Otolaryngologists are often asked to evaluate patients with atypical croup. Atypical patients may present outside the classic age range, with severe or prolonged symptoms, or with multiple episodes of recurrent croup. Evaluation by an otolaryngologist is also warranted when an acquired or congenital abnormality of the larynx and/or trachea is suspected. Ideally, direct laryngoscopy and rigid bronchoscopy are performed approximately 4 weeks after resolution of the acute illness so that acute and chronic components of airway narrowing may be accurately differentiated.

Epiglottitis (Supraglottitis)

Epiglottitis, or supraglottitis, is a diffuse, bacterially mediated inflammation of the supraglottic larynx. After a dramatic decline in the incidence of epiglottitis during the mid 1990s, new-found public skepticism of childhood vaccinations has brought the discussion—and diagnosis—of epiglottitis back to the mainstream.

Epidemiology

Before widespread vaccination, incidence of acute epiglottitis ranged from 6 to 34 cases per 100,000 persons per year.15 Reported cases dropped by more than 90% after the introduction vaccines for Haemophilus influenzae type b (Hib). In 2004, estimates ranged from 0.02 cases to 0.77 cases per 100,000 persons.16 Though epiglottitis is more common during the winter months, the seasonal variability is not as pronounced as with croup. Most cases occur in children between the ages of 2 and 7 years, with males affected 1.2 to 4 times more commonly than females.4 The average age of affected children has increased in a stepwise fashion over the past 15 years; at many children's hospitals, teenagers present with epiglottitis more commonly than do young children.17

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Pathophysiology

The symptoms of acute epiglottitis are caused by inflammatory edema of the supraglottic mucosa with preservation of patency at and below the glottis. In the prevaccine era, the vast majority of cases were caused by Hib, with nearly half of patients having concomitant Hib infections of the lungs, skin, middle ear, or meninges.18 Affected children often have a history of asthma or allergies, raising the question of whether chronic inflammation may decrease mucosal barriers to bacterial entry.

In the postvaccine era, Streptococcus species have emerged as the leading causes of epiglottitis in many communities, while some studies show continued frequent isolation of Haemophilus species.19Staphylococcus aureusMoraxella catarrhalisKlebsiella pneumoniaePasteurella multocidaPseudomonas, and Neisseria species have all been identified, as have Candida and viral pathogens.17,20 Vaccine failure occurs in 2 to 11% of patients and tends to be concentrated in patients receiving the polysaccharide vaccine rather than the more immunogenic protein conjugate vaccines.20

Clinical Presentation

Pediatric patients have rapid onset of high fever, odynophagia, drooling, and respiratory distress evolving over a period of hours. Generally, children with epiglottitis appear toxic and anxious. The adoption of a “sniffing” or “tripod” position, with the waist flexed and neck extended, is indicative of significant airway obstruction. Clinical signs and symptoms may be more varied in older children and adults, thus requiring a high index of clinical suspicion for diagnosis.

Evaluation and Initial Management

Classically, patients in whom epiglottitis was suspected were left undisturbed in quiet, dark rooms until the operating room could be readied for intubation or tracheotomy. When children present with fulminant epiglottitis, these tenets are still followed at most institutions. Protocols can help ensure the rapid coordination of services and specialists needed to care for infectious airway obstruction (Fig. 14.2).

image

Figure 14.2 Sample emergency department protocol for suspected cases of epiglottitis. CBC, complete blood count; ICU, intensive care unit; IV, intravenous; OR, operating room.

Mask ventilation with orotracheal intubation is attempted first. The orotracheal tube may be left in place, or controlled conversion to nasotracheal intubation or even tracheostomy may be undertaken. Since the mid-1970s, the literature has supported nasotracheal intubation in children due to the morbidity associated with pediatric tracheotomy.21

Once the airway has been secured, further diagnostic work-up may be considered. History may help differentiate epiglottitis from inhalation injury, angioedema, or caustic ingestion. Blood cultures and cultures from the epiglottis are typically performed. Though diagnostic yield is highly variable, blood cultures tend to be more useful than direct swabs of the epiglottis.21 Lateral neck radiographs (Fig. 14.3) have relatively poor sensitivity (70%) and specificity (31 to 64%), and are of limited utility.22

The majority of patients under 10 years of age will require airway intervention, but stable adults and older children have been increasingly managed with careful observation.15,21 Factors associated with the need for intervention include rapid symptom onset, stridor, intolerance of secretions, and diabetes mellitus.23

Definitive Management

Once the airway is controlled, broad-spectrum antibiotic therapy is instituted until culture results are available. Ampicillin/sulbactam or a second-or third-generation cephalosporin is routinely used with good results.16 Retrospective studies have not shown benefit from treatment with steroids, but they are often prescribed in an attempt to decrease airway edema.15 Extubation may be considered in the presence of an air leak around the endotracheal tube or after direct visualization of the epiglottis confirms improvement.

image

Figure 14.3 Lateral neck radiograph demonstrating epiglottis thickening (thumb sign [arrow) and dilation of the hypopharynx [double arrow] in a patient with acute epiglottitis.

Bacterial Tracheitis

Bacterial tracheitis (BT), also known as pseudomembranous croup or bacterial laryngotracheobronchitis, was initially described by Jones et al and Han et al in 1979.24,25 Despite advances in imaging and endoscopy, diagnosis remains difficult, and many patients are unsuccessfully treated for croup before BT is suspected. Because aggressive management of the airway may be necessary to prevent obstruction by thick secretions, prompt recognition and treatment of BT is essential.

Epidemiology

Approximately 2% of children hospitalized for croup are eventually diagnosed with bacterial tracheitis. Estimated incidence is less than 0.1 cases per 100,000 children per year with a male predominance.26Seasonal variation mimics that of croup. Cases of BT have been reported in children as young as 4 weeks old, but the mean age of affected children is 5.2 years.26 The original literature reported mortality rates ranging from 6 to 40%. While deaths are rare in the era of modern antibiotics and endoscopic airway management, serious complications such as acute respiratory distress syndrome, postobstructive pulmonary edema, or multisystem organ failure may occur in up to one-third of patients.

Pathophysiology

There is considerable evidence to suggest that BT represents a superinfection of the trachea and bronchi in children already affected by viral respiratory illness.24,26 Virally induced impairment of mucociliary clearance and disruption of mucosal barriers are thought to facilitate the entry of bacteria into the mucosal lining of the airways. Thick secretions contribute to airway obstruction and prevent inhaled medications from contacting the respiratory mucosa.24Methicillin-sensitive S. aureus (MSSA) is by far the most commonly identified pathogen. Other implicated organisms include M. catarrhalisH. influenzaeS. pneumoniae, and Branhamella catarrhalis.27

Clinical Presentation

Patients with BT typically experience a prodrome of coryza, hoarseness, and a croup-like cough. After hours to days, an abrupt clinical decline is heralded by the rapid onset of high fever and stridor. Importantly, cough remains a prominent symptom. Unlike epiglottitis, BT tends not to limit the patient's ability to lie flat or tolerate his secretions. Progression of illness is rapid—87% of the patients who require mechanical ventilation are intubated within 24 hours of presentation.26

Evaluation and Initial Management

Any patient with severe respiratory distress should be considered for diagnostic and therapeutic rigid endoscopy and intubation in the operating room. The presence of thick, purulent secretions or pseudomembranes filling the subglottis and trachea is diagnostic of BT. The pseudomembranes of BT separate from the tracheal walls easily, without bleeding, unlike the fixed pseudomembranes seen in diphtheria. The supraglottis may show mild edema, but generally retains a normal appearance.

Radiographs of the neck are often indistinguishable from those of patients with croup, though hazy irregularities within the tracheal lumen may suggest the presence of purulent debris. Chest radiographs show coincident pneumonia in 60 to 100% of patients with BT.24 Laboratory studies show leukocytosis with bandemia. In contrast to epiglottitis, however, blood cultures are uniformly negative.24

Patients with chronic tracheostomy tubes who are suspected of developing BT present a special challenge. Staphylococcal species and gram-negative organisms can be routinely cultured from the tracheal aspirates of these patients, making the differentiation of colonization and infection difficult. Previous culture data should be reviewed, and a change in the dominant organism should raise the index of suspicion for acute infection when symptoms of respiratory infection are present.

Definitive Management

Most patients with BT require formal control of the airway. Frequent suctioning is essential and repeated endoscopy may be needed to clear the trachea of sloughed tissue and debris.27 The need for tracheotomy should be carefully considered in patients with BT. Endotracheal tubes may become obstructed with inspissated secretions, and can be difficult to replace in emergent situations.

Limited evidence suggests there may be a more subacute form of BT that can be safely managed without intubation. Patients suitable for conservative management tend to be older and tend to lack pulmonary involvement at the time of diagnosis. These patients should be closely monitored in the intensive care setting.

The decision to extubate is guided by clinical improvement, a decrease in the quantity of secretions suctioned from the trachea, and the presence of a leak around the cuff of the endotracheal tube. Extubation is often possible within 72 to 96 hours, though longer courses of 5 to 9 days of mechanical ventilation are not uncommon.27

Antibiotic choice should reflect the dominance of MSSA as the causative organism, but should also cover other common respiratory pathogens. Oxacillin or vancomycin is commonly combined with a third-generation cephalosporin for broad initial coverage.2,27 Culture-directed therapy should be employed as soon as possible and continued for 10 to 14 days. The diagnosis of BT in patients with a chronic tracheostomy tube can be challenging, given that the trachea may be colonized by bacteria. In this population, BT should be suspected when the patient develops symptoms of acute infection, increased secretions, or increased ventilator settings, and should be confirmed by tracheoscopy with culture. In addition to culture-directed systemic antibiotics, aerosolized antibiotic therapy may be helpful in this population.

Rare Causes of Inflammatory Airway Obstruction in Children

Diphtheria

Laryngeal diphtheria continues to appear in epidemic fashion in areas where vaccines are not routinely used. Corynebacterium diphtheriae uses mucosal epithelial cells as a platform for elaboration of a potent exotoxin. The toxin causes tissue damage and local necrosis, leading to the formation of characteristic pseudomembranes. Membranes coat the mucosal surfaces of the upper respiratory tract and may cause sudden respiratory compromise if aspirated. Young children are typically affected, with disease in patients over the age of 15 relatively uncommon.28 Treatment consists of prompt respiratory isolation, mechanical removal of the pseudomembranes, and treatment of the patient and exposed contacts with erythromycin or penicillin. Antitoxin should be obtained from the Centers for Disease Control and Prevention for treatment of confirmed cases.

Tuberculosis

Though rare in the antibiotic era, pulmonary tuberculosis may involve the major airways. Children are prone to extraluminal compression by bulky hilar nodes. Intraluminal obstruction may occur when granulomatous material infiltrates the airway walls. Frank respiratory distress and pneumothorax from erosion of a lymph node through the bronchial wall is rare, but life-threatening.29 Surgical intervention consists of intraluminal or extraluminal enucleation of the obstructing nodes. Fibrous stenosis of affected bronchi may occur years later, requiring segmental resection of the involved airways or sequestered segments of lung.29

Wegener Granulomatosis

Wegener granulomatosis (WG) is characterized by the triad of necrotizing granulomatous inflammation, proliferative glomerulonephritis, and vasculitis. Primarily a disease of young adults, WG has been diagnosed in children as young as 8 years old.30 Head and neck manifestations are seen in nearly all patients, with laryngeal and subglottic involvement occurring in 16 to 23% of cases.31 Active patients may have circumferential edema and friable mucosa; non-specific scar tissue may be the only finding in patients in remission. A positive serum c-anti-neutrophil cytoplasmic antibody is specific for WG, and diagnosis is confirmed with biopsy. Treatment options include glucocorticoids, immunosuppressants, laser ablation, airway reconstructive surgery, or tracheostomy. Approximately 50% of patients require surgical airway intervention.30,31

Sarcoidosis

Sarcoidosis is a chronic inflammatory condition that causes the formation of noncaseating granulomas. Most commonly seen in young adults, sarcoidosis may also present in young children with a triad of uveitis, arthritis, and rash. The pathophysiology is related to persistent T-cell activation and cytokine release. The lungs and lower airways are most commonly affected, but the larger airways and larynx may also be involved.29 The supraglottic tissues are classically thickened, irregular, and edematous. Diagnosis is confirmed with biopsy. Treatment options include systemic or intralesional steroids, cytotoxic agents, and surgical debulking, with tracheostomy reserved for only the most serious cases.

Summary

Historically, inflammatory obstruction of the pediatric airway had devastating consequences. Medical advances that include vaccines, antibiotics, and steroids have led to a dramatic decline in morbidity and mortality attributed to inflammatory airway disease. However, prompt evaluation and management with a low threshold for endoscopy to achieve definitive diagnosis and control of the airway remains essential. Protocols for management of impending airway obstruction are often helpful to ensure the rapid coordination of available of trained personnel, equipment, and services for these patients.

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