Clinical manifestations of laryngopharyngeal reflux.Abstract Laryngopharyngeal reflux (LPR See LPR/LPD. lpr - Line printer. The Unix print command. This does not actually print files but rather copies (or links) them to a spool area from where a daemon copies them to the printer. ) is ubiquitous and associated with many head and neck symptoms and diagnoses. In some cases, the symptom is the diagnosis--for example, LPR can cause sore throat, chronic cough, globus pharyngeus, and laryngospasm. Alternately, LPR can be associated with specific histopathologic lesions--for example, vocal process granulomas. LPR can be the sole cause or an etiologic cofactor cofactor An atom, organic molecule, or molecular group that is necessary for the catalytic activity (see catalysis) of many enzymes. A cofactor may be tightly bound to the protein portion of an enzyme and thus be an integral part of its functional structure, or it may in the development of many disorders of the aerodigestive tract. Introduction This article provides an overview of the protean manifestations of laryngopharyngeal reflux (LPR) (table (1-106)), and it includes a comprehensive list of references. We have intentionally not included all reflux-related conditions. For example, many conditions related to gastroesophageal reflux disease gastroesophageal reflux disease (GERD) Disorder characterized by frequent passage of gastric contents from the stomach back into the esophagus. Symptoms of GERD may include heartburn, coughing, frequent clearing of the throat, and difficulty in swallowing. (GERD GERD gastroesophageal reflux disease. GERD abbr. gastroesophageal reflux disease GERD )--such as reflex bradycardia bradycardia: see arrhythmia. , noncardiac chest pain, esophageal dysmotility, and stricture--are adequately covered in the GERD literature and are not discussed in this article. We have focused primarily on the otolaryngologic manifestations of LPR. The most common symptom of LPR is hoarseness/dysphonia (92%). (6) Koufman reported that patients with intermittent hoarseness often complained of several episodes a year of "laryngitis laryngitis, inflammation of the mucous membrane of the voice box, or larynx, usually accompanied by hoarseness, sore throat, and coughing. Acute laryngitis is often a secondary bacterial infection triggered by infecting agents causing such illnesses as colds, " that lasted for a period of days or weeks. (6) Additional symptoms experienced by most patients included chronic throat clearing (50%), chronic cough (44%), globus pharyngeus (33%), and dysphagia (27%). More than half of these patients denied having any heartburn whatsoever; among the rest, 13% had two or fewer episodes per week, and only 10% complained of more frequent heartburn. Although many patients with LPR experience mild to moderate dysphonia dysphonia /dys·pho·nia/ (-fo´ne-ah) a voice impairment or speech disorder.dysphon´ic dys·pho·ni·a n. Difficulty in speaking, usually evidenced by hoarseness. as their primary symptom, some experience more serious conditions. Less common laryngeal laryngeal /lar·yn·ge·al/ (lah-rin´je-al) pertaining to the larynx. la·ryn·geal or la·ryn·gal adj. Of, relating to, affecting, or near the larynx. manifestations of LPR include laryngospasm, arytenoid arytenoid /ar·y·te·noid/ (ar?i-te´noid) shaped like a jug or pitcher, as arytenoid cartilage. ar·y·te·noid n. 1. fixation, laryngeal stenosis, and carcinoma. (1,3,6,13-38,47-51) LPR is also associated with the development of polypoid degeneration (Reinke's edema), (1,56) vocal fold nodules (figure 1), (1,22,55) and functional voice disorders. (1,52-54) Certain reflux-related conditions are worthy of specific mention and discussion. These conditions include granulomas, paroxysmal paroxysmal (per´  ksiz´ml),adj recurring in paroxysms. laryngospasm, polypoid degeneration, laryngeal stenosis, carcinoma of the larynx, and reflux and functional voice disorders. Granulomas The etiology of laryngeal granulomas is multifactorial multifactorial /mul·ti·fac·to·ri·al/ (mul?te-fak-tor´e-al) 1. of or pertaining to, or arising through the action of many factors. 2. , but LPR should always be suspected as possibly playing a role. Granulomas can occur as a result of the combination of acute mucosal ulceration of the vocal process, LPR, and chronic vocal trauma caused by throat clearing and/or a hard glottal glot·tal adj. Of or relating to the glottis. glottal (glot´ attack. (1,7,39-47) By itself, chronic vocal trauma can lead to vocal fold ulcers and granulomas, but LPR is a cofactor in most cases. The clinician should consider each of the possible contributing etiologic factors and correct each if therapy is to be effective. In the case of granulomas, effective antireflux therapy is sufficient to allow for healing in most patients, as long as vocally abusive behaviors also are corrected. (40,41) Paroxysmal laryngospasm Laryngospasm is an uncommon complaint, but patients who experience this frightening symptom are usually able to describe events in vivid detail. (6,49-51) If the clinician mimics the characteristics of severe inspiratory stridor, the patient will confirm that his or her breathing during an attack does sound similar. Laryngospasm is often paroxysmal, and it usually occurs without warning. An attack wakes some patients from their sleep. In other cases, attacks occur during the day. In some cases, the attacks have a predictable pattern--for example, during exercise. Some patients are aware of a relationship between LPR and their laryngospasm attacks, while others are not. (49) In our experience, most patients with paroxysmal laryngospasm respond well to antireflux therapy; antireflux surgery (fundoplication) is sometimes necessary for patients who fail medical treatment. (7,49,50) In a canine model, Loughlin et al showed that chemoreceptors on the epiglottis epiglottis (ĕp'əglŏt`ĭs): see larynx. responded to acid stimulation at a pH level of 2.5 or less by triggering reflex laryngospasm. (50) The afferent afferent /af·fer·ent/ (af´er-ent) 1. conveying toward a center. 2. something that so conducts, such as a fiber or nerve. af·fer·ent adj. limb of this reflex is supplied by the superior laryngeal nerve superior laryngeal nerve n. A branch of the vagus nerve at the inferior ganglion. At the thyroid cartilage, it divides into two branches, the internal, which supplies the mucous membrane of the larynx above the vocal cords; and the external, which ; nerve interruption abolished the laryngospasm reflex. (50) LPR-induced laryngospasm can also be associated with paradoxical vocal fold movement and even with sudden infant death syndrome sudden infant death syndrome (SIDS) or crib death, sudden, unexpected, and unexplained death of an apparently healthy infant under one year of age (usually between two weeks and eight months old). . (86-92) These areas clearly deserve further research. Polypoid degeneration Polypoid degeneration (Reinke's edema) occurs as a result of chronic laryngeal irritation over a period of many years. It is usually bilateral and occurs most often in elderly women who smoke. It is also seen in nonsmoking patients with LPR and/or hypothyroidism hypothyroidism: see thyroid gland. . Polypoid degeneration can improve with antireflux therapy and smoking cessation, but most patients with these lesions require surgical treatment. It is interesting to note that this group of patients has been reported to have a very high incidence (41%) of prolonged (>4 wk) postoperative dysphonia. (5) This, in part, might have to do with continued (or inadequately treated) LPR after surgery. Most patients with polypoid degeneration have abnormal findings on pH monitoring (pH-metry). (1) Consequently, LPR should be considered in the differential diagnosis. At the very least, patients who undergo vocal fold surgery for this condition should receive intense antireflux treatment prior to surgery and during the perioperative perioperative /peri·op·er·a·tive/ (-op´er-ah-tiv) pertaining to the period extending from the time of hospitalization for surgery to the time of discharge. per·i·op·er·a·tive adj. period. Laryngeal stenosis LPR is the primary cause of subglottic (figure 2) and posterior glottic glot·tic adj. 1. Of or relating to the tongue. 2. Of or relating to the glottis. glottic pertaining to (1) the glottis, or (2) the tongue. stenosis. (1,3,6,13-32) Chronic, intermittent, or chronic-intermittent LPR can cause, or indefinitely perpetuate, laryngeal inflammation. It has been shown in a canine model that intermittent (three times per week only) applications of acid and pepsin pepsin, enzyme produced in the mucosal lining of the stomach that acts to degrade protein. Pepsin is one of three principal protein-degrading, or proteolytic, enzymes in the digestive system, the other two being chymotrypsin and trypsin. to the subglottic region following mucosal injury results in nonhealing ulceration of the cricoid cricoid /cri·coid/ (kri´koid) 1. ring-shaped. 2. the cricoid cartilage. cri·coid adj. Ring-shaped. cricoid 1. ring-shaped. 2. and in subglottic stenosis. (24) LPR documented by pH-metry has been found in 92% of stenosis cases. (6) In our experience, aggressive antireflux treatment coupled with gentle precision surgical intervention is highly effective in the care of these patients. Carcinoma of the larynx The most important risk factors for the development of laryngeal carcinoma are tobacco and alcohol use, but LPR also appears to be an important cofactor, especially in nonsmokers. (1,6,33-38) Koufman reported 31 consecutive cases of laryngeal carcinoma; LPR was documented in 84%, but only 58% overall were active smokers. (6) The exact relationship between LPR and malignant degeneration remains to be proved, but the available [blank.sub.p.H]-metry data suggest that most patients who develop laryngeal malignancy both smoke and have LPR. (33) In addition, leukoplakia leukoplakia /leu·ko·pla·kia/ (-pla´ke-ah) 1. a white patch on a mucous membrane that will not rub off. 2. oral l. atrophic leukoplakia lichen sclerosus in females. and other premalignant-appearing lesions can resolve or partially regress with antireflux therapy. (6) Tobacco and alcohol adversely influence almost all of the body's antireflux mechanisms. They delay gastric emptying, they decrease both upper and lower esophageal sphincter lower esophageal sphincter n. A ring of smooth muscle fibers at the junction of the esophagus and stomach. Also called cardiac sphincter. pressures and esophageal motility motility /mo·til·i·ty/ (mo-til´ite) the ability to move spontaneously.mo´tile Motility Motility is spontaneous movement. , they decrease mucosal resistance, and they increase gastric acid secretion. As a result, smokers and frequent drinkers are strongly predisposed to reflux. The use of [blank.sub.p.H]-metry, followed by antireflux treatment, is recommended for all patients who have laryngeal neoplasia, regardless of the presence or absence of other risk factors. (6,33). Reflux and functional (nonorganic) voice disorders The term functional voice disorder applies to a variety of vocal abuse, misuse, and overuse syndromes. These conditions are also called muscle tension dysphonias, because abnormal patterns of laryngeal biomechanics are seen on fiberoptic laryngoscopy. The most common pattern is supraglottic contraction--either anteroposterior anteroposterior /an·tero·pos·te·ri·or/ (-pos-ter´e-er) directed from the front toward the back. an·ter·o·pos·te·ri·or adj. Abbr. AP 1. Relating to both front and back. contraction (foreshortening foreshortening, n See distortion, vertical. of the vocal folds), false vocal fold approximation/compression (plica plica /pli·ca/ (pli´kah) pl. pli´cae [L.] a fold. pli·ca n. pl. pli·cae 1. A fold or ridge, as of skin or membrane. 2. See false membrane. ventricularis), or both. (52-44) Functional voice disorders are often associated with the secondary development of histopathologic changes in the vocal folds--including hematomas, nodules Nodules A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch. Mentioned in: Leprosy , ulcers, granulomas, and Reinke's edema. Some [blank.sub.p.H]-metry data suggest that 70% of patients with these functional lesions have LPR in addition to abnormal laryngeal biomechanics. (1,52) In our experience, antireflux treatment will resolve vocal fold nodules in many patients who have LPR. Table. Clinical manifestations reported to be related to LPR Type of mainfestation Reference Laryngeal Reflux laryngitis 1-12 Subglottic and tracheal stenosis 1,3,6,13-32 Carcinoma of the larynx 1,6,33-38 Endotracheal intubation injury 6,28 Contact ulcers and granulomas 1,7,39-47 Posterior glottic stenosis 6,24 Arytenoid fixation 47,48 Paroxysmal laryngospasm 6,49-51 Paradoxical vocal fold movement 52-54 Vocal fold nodules 1,22,55 Polypoid degeneration 1,56 Laryngomalacia 57-61 Recurrent respiratory papillomas 1,62 Pachydermia laryngis 2,6,11 Recurrent leukoplakia 6 Pharyngeal Globus pharyngeus 4,6,47,63-66 Chronic sore throat 6,47,66 Dysphagia 6,47,66 Zenker's diverticulum 67 Pulmonary Chronic cough 68-71 Exacerbation of asthma/COPD * 68,69,72-82 Bronchiectasis 68,69 Aspiration pneumonia 83-85 Miscellaneous Sudden infant death syndrome 86-92 Sinusitis 93-97 Otitis media 98-101 Obstructive sleep apnea syndrome 102,103 Dental erosions 104-106 * Chronic obstructive pulmonary disease. 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