Aspiration Syndromes

Aspiration syndromes include all conditions in which foreign substances are inhaled into the lungs. Most commonly, aspiration syndromes involve oral or gastric contents associated with gastroesophageal reflux (GER), swallowing dysfunction, neurological disorders, and structural abnormalities. The volume of refluxate may be significant, usually causing acute symptoms associated with the penetration of gastric contents into airways, or there may be episodic incidents of small amounts of oral or gastric reflux or saliva that enter the airways causing intermittent or persistent symptoms.

GER is very common in infants and children and has been associated with a spectrum of pediatric problems; however, the percentage of reflux that causes respiratory complications is unknown. In 1912, Sir William Osler described the relationship between asthma and GER by stating that "attacks may be due to direct irritation of the bronchial mucosa or... indirectly, too, by reflex influences from stomach." Recent literature describes GER and aspiration syndromes as common occurrences with increasing diagnostic rates. Swallowing dysfunction in conjunction with GER is more likely to cause respiratory symptoms than GER symptoms alone. Eosinophilic GI disorders (eg, eosinophilic esophagitis, gastroenteritis) may also manifest similarly to GER but are refractory to traditional reflux therapies.

Joint clinical practice guidelines for evaluation and treatment of GER in infants and children have been developed by The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). ^[1]

Swallowing dysfunction is a known etiology of aspiration in children. Divided into 4 distinct phases, swallowing is a complex action that involves 5 cranial nerves and 26 muscles. The mouth, pharynx, larynx, and esophagus are involved in a coordinated effort to induce swallowing. Any anatomic, neurologic, or physiologic defect in the swallowing mechanism during the preparatory, oral, pharyngeal, or esophageal phases may lead to aspiration.

Cricopharyngeal dysfunction, cricopharyngeal incoordination of infancy, and transient pharyngeal muscle dysfunction are well described in the pediatric literature. Cricopharyngeal dysfunction involves cricopharyngeal muscle spasm or achalasia of the superior esophageal sphincter. Cricopharyngeal incoordination of infancy is noted in infants who have a normal suck reflex but have incoordination during swallowing; this is possibly secondary to delayed maturation of swallowing reflexes or may be associated with cerebral palsy.

Neurological disorders, including congenital and progressive diseases, may manifest as aspiration syndromes in infants and children. Isolated superior laryngeal nerve damage, vocal cord paralysis, cerebral palsy, muscular dystrophy, and Riley-Day syndrome (ie, familial dysautonomia) are a few of the neurological disorders associated with increased risk of aspiration.

Anatomic disorders, such as cleft palate, laryngeal cleft, esophageal atresia, tracheoesophageal fistula, duodenal obstruction, or malrotation, may have associated aspiration risk. Other conditions such as macroglossia, micrognathia, and laryngeal cleft may predispose patients to aspiration. Motility disorders, such as achalasia or connective-tissue disorders, are associated with increased risk of aspiration.

Studies in humans and animal models revealed that aspiration of acidic content (pH < 2.5) into the lungs causes mucosal desquamation, damage to alveolar lining cells and capillaries, and acute neutrophil inflammation. ^[2]

The act of swallowing is divided into the following 4 discrete phases: oral preparatory, oral propulsive, pharyngeal, and esophageal:

• The oral preparatory phase begins when foods and liquids are placed into the mouth, mixed with saliva, and formed into a bolus.

• The oral propulsive phase consists of moving the bolus into the pharynx, triggering the reflex swallow, which is the major component of the pharyngeal phase.

• During the pharyngeal phase, the larynx elevates and closes at the level of the epiglottis, aryepiglottic folds, and true and false vocal cords. Normally, the laryngeal reflex during the pharyngeal phase of swallowing acts as a protective mechanism against direct or indirect aspiration.

• The esophageal phase is initiated when the bolus passes through the relaxed cricopharyngeal muscle and enters the esophagus.

Aspiration may occur when foreign substances enter the hypopharynx, either before relaxation of the cricopharyngeal muscle or before closing of the laryngeal sphincters. In patients with neurological disorders that affect swallowing, the absence of a swallowing reflex within 30 seconds of the completion of the oral preparatory phase results in direct aspiration. Direct aspiration is the aspiration of a food bolus while swallowing, whereas indirect aspiration is the reflux of food from the stomach into the esophagus and pulmonary system.

Patients with structural abnormalities, such as H-type tracheoesophageal fistula, duodenal atresia, and achalasia, may have problems with direct aspiration, indirect aspiration, or both. Patients with H-type tracheoesophageal fistulas often aspirate pharyngeal secretions. If the fistula is distal, indirect aspiration of gastric contents is a risk. Patients with malrotation may have GER with associated aspiration risk.

GER is often caused by transient lower esophageal sphincter (LES) relaxation. Other mechanisms include a low resting LES pressure and increased intragastric pressure. Increased intra-abdominal pressure due to coughing raises the gastroesophageal pressure gradient and increases the risk of reflux. However, GER may be the etiology of chronic cough. This cause-and-effect relationship may be difficult to elucidate.

Several mechanisms, including the cough reflex, pulmonary macrophages, and the mucociliary escalator, are protective if aspiration occurs. If any of these actions are absent, impaired, or overwhelmed, chronic or acute aspiration symptoms may occur. The extent of injury is related to the amount and characteristics of the aspirate, the frequency of occurrences, and the effectiveness of protective lung-clearance mechanisms.

Model and Boysen reviewed the pathophysiology of pulmonary aspiration of stomach contents. ^[3]  Laboratory studies revealed that aspiration of significant amounts of gastric contents, regardless of the nature of the aspirate, causes acute respiratory insufficiency and chemical pneumonitis. Acidic refluxate with pH less than 2.5 appears to be the most caustic to the pulmonary system. Histologically, one may see damage to alveolar lining cells and capillaries, as well as bacterial invasion, mucosal desquamation, and mononuclear cell inflammation.

Respiratory symptoms due to aspiration of gastric contents may occur via several mechanisms. A vagally mediated reflex bronchospasm occurs in response to gastric acid irritation of the distal esophageal mucosa. Thus, reversible bronchospasm often occurs without documented indirect aspiration. Other potential mechanisms include heightened bronchial reactivity and microaspiration. However, as many as 70% of patients with pharyngeal dysphagia with aspiration have no obvious clinical signs of coughing, gagging, or choking. Chronic lung hyperinflation with flattening of the diaphragm decreases the protective reflux barrier of the diaphragm. An increased transdiaphragmatic pressure gradient predisposes to the movement of gastric contents into the esophagus.

Medications used to treat asthma may contribute to symptoms. Beta-agonists and methylxanthines decrease the LES tone. Aminophylline is known to increase gastric acid secretion. Angiotensin-converting enzyme (ACE) inhibitors and inhaled corticosteroids have been reported to cause chronic cough.

Apnea, obstructive and central, has also been associated with aspiration of gastric contents. Laryngospasm manifests as obstructive apnea secondary to reflux. Classically, obstructive apnea occurs within one hour after a feed when a patient suddenly stops, becomes apneic, stares, and develops a rigid opisthotonic posture. Continued ineffective respiratory effort is observed, but coughing or gagging is not necessarily present. If this progresses, pallor, cyanosis, and possible hypotonia ensue. The complete obstruction of the larynx impedes air movement, causing an obstructive picture. If incomplete laryngeal obstruction occurs, stridor may be noted during the examination. Central apnea has also been noted as a result of reflux. The superior laryngeal nerve has been implicated in this mechanism. Central apnea can be differentiated from obstructive apnea by the lack of respiratory effort observed.

Chronic inflammation of the larynx and subglottic space from recurrent aspiration may cause stridor and hoarse voice.

United States statistics

Medical practitioners are diagnosing GER and its respiratory complications more frequently now than in the past. Theories of the increased frequency of GER diagnosis include an increased prevalence of pathologic GER, improvement in diagnostic tests for GER, misdiagnosis, and overdiagnosis. The increase in diagnostic rate probably is multifactorial, but factors such as formula feeding, increased volume of feeds, and prolonged use of infant seating devices in infants too young to sit have been suggested as epidemiologic causes for this increase. ^{[4, 5]}

In a study of the diagnostic rate of GER in Army hospitals over a 25-year period (1971-1995), the total diagnoses of GER increased 20-fold, with 84% of cases in infants younger than 6 months. ^[6] The diagnostic rate for GER diagnosis rose from 0.74 in 1000 persons in 1971 to 8.16 in 1000 persons in 1995. Orenstein states that 40% of healthy infants regurgitate more than once a day, and as many as 20% of children reflux to the extent that parents feel it is a problem. ^{[7, 8, 9]} Nelson et al (1998) described that most infants outgrow this physiologic reflux but that as many as 5% of infants have persistent reflux symptoms. ^[10]

Approximately 7% of infants have reflux severe enough to be brought to a physician's attention. As many as 40-50% of infants with GER present with respiratory symptoms. Approximately 25-80% of children with asthma have GER, ^[11] but as many as one third of patients with pulmonary symptoms of GER have no esophageal symptoms.

Incidence of eosinophilic GI disorders has increased during the past decade. Eosinophilic esophagitis has been diagnosed in approximately 2 of 10,000 children in the Cincinnati region. ^[12] Another group of investigators noted that 1% of patients with esophagitis have eosinophilic esophagitis.

The incidence of swallowing dysfunction associated with aspiration syndromes is not known because clinical signs of aspiration may be quite subtle. As many as 70% of patients with pharyngeal dysphagia with aspiration have silent aspiration (ie, no overt clinical signs during aspiration). Sheikh et al published a retrospective review of 112 neurologically normal infants with chronic respiratory symptoms who underwent videofluoroscopic-modified barium swallow study. Almost 12% had evidence of swallowing dysfunction and silent chronic aspiration without evidence of gastroesophageal reflux. ^[13] . Laryngeal penetration visualized by videofluoroscopic swallowing has recently been associated with an increased incidence of pneumonia in children as compared to children with no evidence of penetration or aspiration. ^[14]

The incidence of aspiration syndromes associated with anatomic or neurologic disorders is unknown. The incidence of an isolated cleft palate is approximately 0.5 per 1000 live births, whereas the incidence of cleft lip and palate differs by ethnicity. Patients with a cleft palate are at risk for aspiration secondary to an abnormal communication with the nasal and oral cavities. Nasopharyngeal reflux commonly is observed in patients with cleft palate with or without associated cleft lip. Unilateral or bilateral vocal cord paralysis accounts for approximately 10% of all congenital laryngeal lesions. Esophageal atresia occurs in 1 per 3000-4000 live births, with 85% associated with tracheoesophageal fistulas. Patients with vocal cord paralysis and laryngeal clefts were noted to have increased incidence of laryngeal penetration and increased incidence of pneumonia and aspiration. ^[14]  

International statistics

International data on frequency of aspiration syndromes are not available.

Race-, sex-, and age-related demographics

In Whites, cleft lip and palate occurs in approximately 1 in 1000 births; in Asians, it occurs in approximately 2 in 1000 births. In Blacks, the incidence of cleft lip and palate is approximately 0.41 in 1000 births.

One study revealed an increased incidence of GER in males over females, but no strong prevalence in one sex has been observed. Cleft lip and palate are seen more commonly in males than in females, with approximately 60-80% incidence in males. Isolated cleft palates occur more frequently in females.

Physiologic GER (ie, benign regurgitation) occurs most commonly in the first few months of life but generally resolves by age 1-2 years. Approximately 84% of patients diagnosed with GER in Army hospitals in a 25-year period were younger than 6 months. ^[6] Patients with anatomic, physiologic, or neurologic disorders associated with aspiration are often diagnosed early. Esophageal atresia with or without tracheoesophageal fistula may be diagnosed in the delivery room or shortly after birth. The prevalence of respiratory complications of GER in infants and children by age is not known.

In general, the prognosis for an infant or child with an aspiration syndrome is good; but this depends partly on the underlying disorder. GER spontaneously resolves in most children by age 1-2 years.

Morbidity/mortality

Patients with an aspiration syndrome are at risk for severe respiratory sequelae and, possibly, death. Patients with a massive aspiration event have a mortality rate of 25%. ^[15]  One study by Kohda et al examined 72 infants with documented aspiration by fluoroscopy for etiology of the aspiration and prognosis. ^[16]  None of the patients without underlying neurologic disorders had evidence of aspiration after one year. In patients with neurological disorders, two thirds of patients had prolonged aspiration on follow-up. In patients who initially presented with a near-miss sudden infant death syndrome, or acute life-threatening episode (ALTE), 3 of 13 patients had prolonged aspiration.

No standard case definition of GER disease is recognized; thus, morbidity statistics are difficult to interpret. In 1959, Carre studied the natural history of severe GER and found that less than 5% of clinically affected patients died as a consequence of reflux. ^[17]

Complications

Chronic lung disease may develop from repeated aspiration of refluxate.

Pulmonary fibrosis may occur over time secondary to repeated aspiration of small volumes of gastric secretions, promoting a progressive fibrotic pulmonary response.

Chronic bronchitis and bronchiectasis are also recognized complications.

Educate patient and family regarding basic and conservative measures to prevent GER and ensuing complications.

For patient education resources from eMedicineHealth, see the Digestive Disorders Center, as well as Bronchoscopy.