**2.1 Chronic laryngitis and laryngopharyngeal reflux (LPR)**

Patients with reflux laryngitis often have characteristic anamnestic data and records in the history of the disease. Common symptoms of laryngitis include chronic or intermittent recurrent cough, chronic sore throat, hoarseness, clearing of the throat, dry mouth, feeling of a 'lump' and tickling in the throat, nocturnal dyspnea, laryngospasm and dyspepsia. Inspection of the laryngeal mucosa may reveal erythema and edema of the mucosa covering the arytenoid cartilage, the posterior part of the larynx, and often the posterior part of the true vocal cords.

Two theories explain the pathogenesis of reflux laryngitis:


Due to direct injury to the laryngeal and pharyngeal mucosa, mucociliary transport is damaged and secretions accumulate in the throat, which causes additional irritation of the mucosa and contributes to the symptoms of postnasal drip, throat clearing and foreign body sensation in the throat. As the larynx lacks the protective external cleansing and salivary mechanisms that neutralize acid, gastric reflux remains undiluted for a long time, resulting in tissue injury. The action of pepsin leads to the depletion of the carbonic anhydrase isoenzyme III, and it catalyzes the reversible hydration of carbon dioxide resulting in the production of bicarbonate ions. The formation of bicarbonate ions directly neutralizes the acidic stomach contents and inactivates pepsin, so the ions actually protect the tissue from acid refluxate [3, 4]. On the other hand, depletion of carbonic anhydrase isoenzyme III reduces the neutralization of acidic gastric contents and allows its prolonged activity. According to the reflex theory, laryngopharyngeal reflux occurs due to esophageal reflux that stimulates vagal-mediated reflexes, resulting in a subjective need to 'clear' the throat and a chronic cough that leads to injury to the laryngeal mucosa. Laryngopharyngeal reflux is a clinical entity that represents the return of gastric contents to the space of the larynx and hypopharynx, which causes the contact of acid with the tissues of the upper aerodigestive tract [5]. In the physiological state, the upper and lower esophageal sphincters act together and prevent reflux of gastric contents into the esophagus and upper aerodigestive tract. Howewer, the pathophysiology of LPR is typically attributed to a defect or dysfunction of the upper esophageal sphincter. The esophagus features a number of protective mechanisms which prevent injury of the mucosa, which the laryngopharyngeal mucosa do not possess, and are more susceptible to damage from acid reflux. Laryngeal epithelium is up to 100 times more susceptible to pepsin damage than esophageal tissue [6]. Regurgitation of the contents may cause primary burning and/or sore throat, cough, need for excessive throat cleansing, and secondarily may cause symptoms such as dysphonia, productive expectoration and globus hystericus (feeling of a 'lump' in the throat). Signs of laryngopharyngeal reflux are visible in the form of laryngeal irritations, hyperemic mucosa of the vocal cords and arytenoids, thinned vocal cords, posterior pharyngeal wall abnormalities, erythema, edema, and discontinuity of mucosal continuity. Of these symptoms, laryngeal irritations and abnormalities of the posterior pharyngeal wall have a statistically significant prevalence in patients with reflux. It should be noted that these symptoms, in addition to esophagitis and gastroesophageal reflux disease, are also present in persons exposed to allergens and irritants and in postnasal drip syndrome. Most authors interpret laryngopharyngeal reflux as atypical gastroesophageal reflux, although some authors disagree with this interpretation given the different pathophysiology and symptomatology of these refluxes [7]. It is important to emphasize that the etiology of reflux in laryngopharyngeal and gastroesophageal reflux is not the same, just as the form and circumstances of occurrence are not quite the same. For example, laryngopharyngeal reflux occurs more often during the day in an upright position, while gastroesophageal reflux occurs in a horizontal position and at night, or during sleep. Different body composition of patients with laryngopharyngeal and gastroesophageal reflux [8] was also observed, and published studies show an association between increased body mass index (identified as obesity) and gastroesophageal

reflux disease [9] and a statistically significant higher incidence of gastroesophageal reflux disease in patients with registered obesity. In contrast, increased body mass index is not statistically significant in patients suffering from laryngopharyngeal reflux [10, 11]. Reflux associated with laryngeal symptoms is verified by laryngoscopy and 24-hour pH monitoring. Patients with laryngopharyngeal reflux without alarming symptoms are treated empirically with proton pump inhibitors for one to two months. If this type of therapy is effective, according to individual needs, the therapy is extended to six months with the aim of complete healing of the laryngeal and pharyngeal mucosa.

#### **2.2 Dysphonia**

Chronic gastroesophageal reflux is an etiological factor that contributes to the manifestation of laryngeal symptoms, primarily hoarseness. In addition to hoarseness, laryngopharyngeal reflux and laryngitis may occur. Koufman et al. found that 78% of dysphonic patients have gastroesophageal reflux disease [12]. According to Vashana, acid reflux is especially common in singers. The author explains this statement in several facts: muscle activity due to a vocal technique that works against the lower esophageal sphincter; inadequate feeding and sleep dynamics; emotional components and exposure to stressors typical of this profession [13].

#### **2.3 Chronic rhinosinusitis (CRS)**

More recent studies has reported significant association between gastroesophageal reflux and chronic rhinosinusitis, but the nature of the association is still unknown. Gastroesophageal reflux disease can cause several upper airway symptoms and change the physiology of nasopharyngeal mucosa, while upper airway diseases might also exacerbate GERD symptoms [14]. This associaton can be explained by three physiological mechanisms: the direct effect of acid or acidic vapor in the nasal mucosa, a dysfunction of the autonomous nervous system and the presence of Helicobacter pylori. It is known that the direct contact of the acid with the nasopharyngeal mucosa results in mucosal edema, with reduction of the mucociliary clearance and obstruction of the sinusal ostium. The acid reflux is an uncommon event in the nasopharynx and occurs in only 5% of GERD patients. Autonomic dysfunction, in this case the increase of the vagal tonus, may partly account the hyper-reactivity of the airways to acid. The Heliobacter pylori has been identified in the esophagus, palatine and tonsils, saliva and teeth, and is not known how its presence can result in some abnormalities of this tissues. Retrospective studies describe an improvement of 69 to 89% of the nasosinusal symptoms after GER treatment. Despite this knowlege, it is still not possible to state that the gastroesophageal reflux is one of the leading risk factors to chronic rhinosinuitis, but it must be researched as an unchaining factor when there is no other evident etiology. Howewer, GER symptoms are very prevalent in patients with chronic rhinosinusitis [15].

#### **2.4 Chronic otitis media (COM)**

Chronic otitis media may lead to tympanic membrane perforation as a consequence of unresolved and resistant middle ear infection, blockage of the Eustachian tube, insufficiency of ciliary clearance, or an injury to the ear persisting more than 3 months. Various microorganisms are considered as etiologic agents in COM. Other predisposing factors may also play role in persistence of the disease. Many recent studies have shown a potential association between gastroesophageal reflux

#### *Extraesophageal Manifestations and Symptoms of Esophageal Diseases DOI: http://dx.doi.org/10.5772/intechopen.96751*

and otitis media chronica [16]. Gastroesophageal reflux can be an inflammatory cofactor and can result in upper respiratory tract disorders, including COM in pediatric and adult age group. Otitis media with effusion is the most common cause of hearing loss in children. The pathogenesis is multifactorial: infections, impaired immunologic status, allergic history, anatomical problems, familial predisposition and enviromental factors have role in pathogenesis. The angle and length of the Eustachian tube are more horizontal and shorter in infants than in adults, and may allow reflux of gastric contens from the nasopharynx into the middle ear. It can cause to lay the groundwork for mucociliary clearance dysfunction and bacterial infections. Some studies found pepsin concentrations in samples from middle ear effusions of up to 1000-fold greater in children who undergone myringotomy. It was suggested that the GER may be related to glue ear in children. The therapy of COM is mainly surgical. Higher level of damage in the middle ear of patients having GERD requires appropriate treatment which may positively affect outcomes for COM surgery [17].
