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). 
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. 
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. [3, 4]
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.  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. [6, 7, 8] Nelson et al (1998) described that most infants outgrow this physiologic reflux but that as many as 5% of infants have persistent reflux symptoms. 
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,  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.  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.  . 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. 
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. 
International data on frequency of aspiration syndromes are not available.
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%.  One study by Kohda et al examined 72 infants with documented aspiration by fluoroscopy for etiology of the aspiration and prognosis.  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. 
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.  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.
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