EXTRA ESOPHAGEAL REFLUX AND SYMPTOMS OF THE EAR, NOSE, THROAT (cont'd)

Effects of EER on the larynx, or voice box

The larynx is anatomically just in front of the esophagus and therefore is very susceptible to the effects of EER. Multiple sites of the larynx can be irritated and cause a number of different signs and symptoms. Some of these include: chronic cough, hoarseness with or without vocal cord nodules, laryngeal ulcers, and vocal cord dysfunction.

Cough
Cough is one symptom commonly associated with irritation of the larynx. Cough is a protective reflex that removes irritants or infectious organisms such as those causing pneumonia. Irritants are detected by "cough receptors," which are nerve endings located in the larynx and other parts of the respiratory tree. Receptors are also located in the naso- and oro-pharynx (throat), the sinuses, and the ears (7). Through coughing, the airway tries to relieve itself of its acid load as best as it can. However, persistent cough can itself further irritate the airway. EER is an important agent in chronic cough, that is, coughing that continues for 3-8 weeks. Excluding infectious diseases, EER is third most common cause of chronic cough in children and the most common cause in infants 0-18 months old (8).

Hoarseness
Hoarseness is another symptom that can be associated with the deleterious effects of reflux on the larynx. Hoarseness is a general term for any abnormal voice quality, but voice quality can be further described as breathy or harsh, husky or rough, strident, or coarse. Though voice intensity varies with the amount of a air pressure against vocal cord resistance, voice quality is primarily determined by length, tension, strength of movement, mass, or position of the vocal chords (9). Any aberration of length or tension of the vibrating segment, mass, posture, or strength of the vocal cords may result in hoarseness. In a study of children aged 2-12 years old who had chronic hoarseness for more than 6 months, 70% of them were found to also have GERD (10). When researchers directly examined the vocal cords of these children, one child's vocal cords looked normal, but the remainder had a variety of abnormalities that included cord swelling, nodules (Figure 4), and evidence of healing ulcerations.

Paradoxical vocal cord dysfunction (PVCD)
Another abnormality of the vocal cords that can be associated with damage from reflux is paradoxical vocal cord dysfunction (PVCD). During breathing, normally functioning vocal cords should move into an open position to allow free flow of air through the larynx. In PVCD, the vocal cords are inappropriately closed with breathing. When cord movement is not synchronous with breathing, voice quality isn't affected, but it creates a sensation of airway obstruction. PVCD can be quite distressing and mimic asthma or severe inspiratory airway obstruction. In rare cases, it has resulted in placement of a tracheotomy tube to assist breathing. PVCD is most commonly found in teenagers (11), but cases masquerading as bilateral vocal cord paralysis have been reported in newborns (12). Reflux therapy resolves PVCD and may be curative (11,12).

Stridor and laryngomalacia
Another sign of a problem in the airway is stridor, which is a coarse, high-pitched sound when breathing in. Stridor results from turbulent, rapid air flow through a narrowed portion of the airway. Because a number of airway disorders can cause stridor, a physician should explore all possibilities when evaluating patients with stridor, but EER may play a significant role in those conditions most commonly associated with stridor.

Airway abnormalities present at birth are responsible for 87% of stridor cases in infants (13). The most common of these congenital abnormalities is laryngomalacia (13). Laryngomalacia refers to an abnormal floppiness of the laryngeal tissues just forward of the vocal cords at the airway entrance. Stridor results because upon inspiration, these floppy tissues get pulled into the opening of the airway, narrowing the diameter of the opening by partially blocking it (Figure 4). Although inspiratory breathing is noisy, breathing on expiration is normal, as is the voice.

Parents may notice their baby has noisy breathing at birth, but usually laryngomalacia-associated stridor becomes most noticeable at 1-2 months when the infant is becoming more active and making more demands on the airway. Respiratory effort and noisy breathing typically get worse before they resolve, usually by 18 months of age.

Two studies have shown a strong association between laryngomalacia and gastroesophageal reflux. In one study, 80% of infants with stridor due to laryngomalacia also had gastroesophageal reflux (14). In another, more recent study, the severity of laryngomalacia was shown to be directly related to the severity of gastroesophageal reflux (15).

The co-association of laryngomalacia and reflux may be a common manifestation of neuromuscular immaturity that simultaneously results in flaccid airway structures and poor esophageal sphincter tone (14), which may explain why symptoms often disappear as the child matures. Another possibility is that EER is a secondary effect of the laryngomalacia in which the inspiration of air against the narrowed airway creates of suction effect that pulls reflux up and out of the esophagus (14). Either way, reflux can cause a worsening of symptoms of laryngomalacia because the inflammation and swelling of the laryngeal tissues results in still greater obstruction of the airway. Aggressive reflux therapy is recommended (5).

Croup and subglottic stenosis (SGS)
Reflux may also play a role in children who suffer from repeated cases of croup. Symptoms of croup include stridor, a barking cough, hoarseness, and difficulty breathing. In children older than a year, an isolated case of croup often comes on the heels of an upper respiratory infection and is usually due to a virus-induced inflammation of the larynx. However, infants less than 1 year old who have repeated cases of croup may have a condition called subglottic stenosis (SGS), which is an abnormal narrowing of the subglottis, a region of the larynx located below the vocal cords (Figure 4). Different severities of SGS exist and are graded 1-4, with a Grade 1 being the least severe and Grade 4 representing nearly complete obstruction of the airway.

Infants can be born with SGS, but they can also develop SGS due to physical injury to the larynx. Physical injury includes damage caused by acid reflux. Studies in animals in which direct application of acid to the larynx resulted in the formation of SGS confirms a causal association between EER and acquired SGS (16). One study has shown that infants who have recurrent cases of severe croup requiring hospitalization are more likely to have an additional diagnosis of reflux (17), and another reported that 80% of children undergoing surgery to repair their SGS had at least one positive test for EER (18).

A mild, Grade-1 SGS that would normally not be noticed can be exacerbated by EER or recurrent viral illness. Children with Grade-1 SGS may spontaneously improve as they get older, and often anti-reflux medication is all that is needed to keep the airway sufficiently open until the SGS resolves. Severe SGS requires surgical intervention, but anti-reflux medications help improve the success rate of these surgeries and reduce the need for additional operations, presumably because healing can occur more readily in the absence of acid (19, 20).