pharyngeal complications.doc

此文档收集于网络，如有侵权，请联系网站删除PART 1 Oral cavity, pharynx and esophagusGI Motility online (2006) doi:10.1038/gimo46Published 16 May 2006Laryngeal and pharyngeal complications of gastroesophageal reflux diseaseGregory N. Postma, M.D. andStacey L. Halum, M.D.Key Points When reflux disease involves the larynx or pharynx, it is referred to as laryngopharyngeal reflux (LPR) or extraesophageal reflux, rather than gastroesophageal reflux disease (GERD). Laryngopharyngeal reflux and GERD are two related, yet different, disease states with different risk factors, pathophysiology, treatment, and outcomes. Patients with LPR infrequently have significant heartburn, and most commonly present with laryngeal symptoms such as hoarseness, globus sensation, throat clearing, sensation of postnasal drip, difficulty swallowing, chronic cough, and laryngospasm. Serious complications of LPR include obstructive pathology, such as laryngeal granulomas, subglottic/glottic stenosis, laryngospasm, and even laryngeal carcinoma. Although the complications of LPR may require surgical management, aggressive perioperative reflux therapy should be initiated if the patient is to achieve an optimal outcome.Top of page Laryngopharyngeal Reflux (LPR)Gastroesophageal reflux involves the backflow of stomach contents into the esophagus. In some cases the gastric refluxate reaches the larynx or pharynx, which is called laryngopharyngeal reflux (LPR). Other synonyms that have been used for LPR include extraesophageal reflux, atypical reflux, gastropharyngeal reflux, laryngeal reflux, pharyngoesophageal reflux, and supraesophageal reflux. Using prolonged pH monitoring, the diagnosis of gastroesophageal reflux disease (GERD) is typically not made unless a patient exhibits over 45 reflux episodes or has elevated acid exposure times at the esophageal probe (Table 1). Esophageal acid exposure times below this are considered normal or physiologic esophageal reflux. In contrast, one or two episodes of acid exposure (pH 4) at the proximal probe located in or above the upper esophageal sphincter (UES) is accepted as diagnostic of LPR. Although these diagnostic criteria for GERD and LPR may vary across institutions, the contrasting pH probe criteria for LPR and GERD is a common theme, because laryngeal and pharyngeal mucosa are much more susceptible to acidic injury than esophageal mucosa.Table 1: pH probe criteria for diagnosis of gastroesophageal reflux disease Full size tableAlthough some patients meet pH probe criteria for both GERD and LPR, many have LPR or GERD alone. Over recent decades, studies have shown LPR and GERD to be two unique but related disease entities, with different risk factors, symptoms, pathophysiology, and responses to therapy.1, 2, 3, 4, 5, 6 Furthermore, the diagnostic modalities for the evaluation of LPR are different from those for GERD.Patient risk factor profiles and complaints differ greatly from LPR patients to GERD patients. For example, obesity is not associated with isolated LPR; however, it has a strong association with GERD and it is an independent risk factor for GERD symptoms and erosive esophagitis.4, 5 Patient complaints also differ from LPR to GERD patients. One landmark study demonstrated that 100% of otolaryngology patients with reflux complained of hoarseness, but only 6% of them reported heartburn.6 In contrast, the same study demonstrated that 89% of gastroenterology patients with reflux reported heartburn, and none of them complained of hoarseness.Esophageal motor function has also been shown to differ between LPR and GERD patients. In one study, esophageal acid clearance time was significantly longer in patients with GERD (isolated or in combination with LPR) than in patients with isolated LPR.2 In addition, the difference in acid clearance between LPR patients and normal individuals was not statistically significantly different. This suggests that differences in pathophysiology between LPR and GERD patients are part of the basis for the contrasting symptomology. Not only is esophageal motility generally different between LPR and GERD patients, but reflux patterns on pH probe studies demonstrate that LPR patients are more likely to have reflux in an upright position whereas GERD patients are more likely to reflux in a supine position.1Both LPR and GERD can be evaluated by a variety of diagnostic tests, including barium esophagography, radionucleotide scanning, the Bernstein acid perfusion test, esophagoscopy with biopsy, impedence testing, and pH probe monitoring. In addition, the clinical evaluation of LPR generally involves a flexible (or rigid) laryngoscopy examination, and laryngeal sensory testing may be added. Although dual pH probe testing is reasonably sensitive and specific for reflux events, the other diagnostic modalities, such as barium esophagography, radionucleotide scanning, and the Bernstein acid perfusion test, have a low sensitivity and therefore have been largely abandoned as diagnostic tests of choice for reflux. Multichannel intraluminal impedance testing is a newer modality that allows detection of both acidic and nonacidic reflux events, and has shown excellent sensitivity in GERD populations, but its role in LPR patients remains to be determined.7Perhaps the greatest difference in diagnostic testing for GERD and LPR patients is the role of esophagoscopy with biopsy. Although esophagitis is found in only 12% patients with LPR,3 it is considered the sine qua non of GERD. In fact, most uncomplicated GERD patients never require pH probe testing or esophagoscopy for diagnosis and are simply followed empirically for symptom improvement.8 Because of the low rate of significant esophagitis among LPR patients, either trials of empiric antireflux therapy or pH probe testing are generally warranted as the initial diagnostic steps. Esophagoscopy in LPR patients whether transnasal esophagoscopy (TNE) or traditional has been reserved for patients with symptoms of both LPR and GERD, patients with other risk factors for esophageal pathology such as Barretts esophagus, patients requiring chronic antireflux therapy, and patients with pulmonary manifestations such as chronic cough. However, a provocative report from Reavis et al.9 suggests that esophageal screening for Barretts metaplasia is important for patients with LPR and chronic cough. In this retrospective paper, individuals with LPR symptoms had a greater prevalence of esophageal dysplasia and cancer than patients with classic GERD symptoms.Response to antireflux therapy is another major contrast between LPR and GERD patients. The GERD symptoms and esophagitis are often well controlled with once-daily proton pump inhibitor (PPI) therapy with rapid relief of symptoms usually in less than 2 weeks. Daily PPI therapy has been shown to last for less than 14 hours if given in the morning, and an evening dose may last less than 10 hours.10 Although this coverage may be adequate for esophageal healing, the laryngeal mucosa is much more susceptible to refluxate injury, and therefore often requires twice daily (24-hour) PPI coverage.11, 12 Furthermore, GERD symptoms may improve rapidly after initiating PPI therapy, whereas LPR symptoms often take several months to resolve.1, 13Top of page History of Laryngopharyngeal RefluxWith the introduction of ambulatory pH monitoring, manometry, and flexible fiberoptic esophagoscopy in the 1960s, evidence-based research regarding GERD rapidly expanded. In 1968, acid-related laryngeal ulcerations and granulomas (Figure 1) were first reported in the otolaryngology literature. Subsequent studies suggested that acid reflux might be a contributory factor in hoarseness, globus pharyngeus, dysphagia, chronic cough, otalgia, and laryngospasm. Acid reflux also was implicated as a potential etiology in various laryngeal diagnoses such as posterior laryngitis, laryngeal stenosis,14 and laryngeal carcinoma.Figure 1:Laryngeal granulomas in a patient with numerous episodes of pharyngeal acid exposure and no history of intubation. Full size image (50 KB) Download Power Point slide (2,468 KB) The landmark study by Koufman1 in 1991 demonstrated abnormal acid reflux on dual pH probe testing in 62% of 182 patients with laryngeal carcinoma, stenosis, laryngitis, globus pharyngeus, dysphagia, and chronic cough. Only 43% of the patients had symptoms of heartburn or regurgitation, whereas most of them had laryngopharyngeal symptoms. Many of the patients (n = 128) also underwent barium esophagography with videofluoroscopy, with dysmotility being detected in 12% and spontaneous gastroesophageal reflux (GER) in only 9%. After 6 months of antireflux therapy with behavioral modification and aggressive H2-antagonist therapy, 85% of the patients available for follow-up (n = 123) had resolution of their LPR symptoms. More important, the study included an animal model that demonstrated that more severe inflammation resulted when a preexisting subglottic mucosal injury was repeatedly treated topically with pepsin and acid (up to pH 4) when compared with acid alone or controls. Thus, it was made clear that acid alone was not the sole source of injury in reflux disease, but rather acid and active pepsin.Top of page EpidemiologyAlthough the prevalence of LPR in the general population is not known, the prevalence of reflux among patients with laryngeal and voice disorders has been estimated to be about 50%.15 In contrast to GERD patients, patients with isolated LPR are not obese.4, 5 Unfortunately, the remaining risk factors and patient profiles for LPR are not well established because epidemiologic studies in this area are lacking.Top of page PathophysiologyThe etiology of reflux events that occur with LPR are largely unknown, although UES dysfunction has been hypothesized as a possible factor. Although esophageal dysmotility and lower esophageal sphincter dysfunction play important roles in GERD, they appear to have less of a role in LPR. Furthermore, manometry, including the pharynx and UES, demonstrates that patients with LPR often have normal esophageal motility.1, 2 Unlike GERD, which primarily involves supine (nocturnal) reflux events, LPR reflux occurs frequently in the upright position. The reflux events in LPR also tend to be brief relative to the prolonged events that occur with GERD.1, 6The laryngeal damage that occurs in LPR is not caused by acid alone, but it requires both acid and activated pepsin, and it must be remembered that pepsin remains active over a pH of 5.0.1, 16, 17 When compared to the esophageal mucosa, the laryngeal mucosa is injured with much lower levels of acid/pepsin exposure. It has been accepted that the extrinsic defense mechanisms between the laryngopharynx and the esophagus are markedly different, with the latter having much more resistance to acid peptic exposure. In fact, the intrinsic defense mechanisms of the laryngeal and esophageal mucosa are different as well. For example, one of the carbonic anhydrase (CA) isoenzymes, CA III, has been shown to have increased expression in the esophageal mucosa in response to refluxate exposure, whereas the larynx demonstrates a depletion of CA III after chronic reflux exposure. Furthermore, although esophageal mucosal response to acid/pepsin exposure appears to often be readily reversible, laryngeal mucosa can easily be damaged irreversibly.16, 17Top of page History and SymptomsPatients with LPR commonly present with complaints such as hoarseness, globus sensation, throat clearing, sensation of postnasal drip, difficulty swallowing, chronic cough, choking episodes/laryngospasm, and (occasionally) heartburn. These items have been included in the reflux symptom index (RSI), which is a validated clinical tool for LPR18 (Table 2). Often patients report a long history of LPR symptoms, gradually worsening with time. Occasionally an event such as endotracheal intubation, vocal abuse, or an upper respiratory infection leaves the patient dysphonic, with the patient having increased awareness of the full spectrum of LPR symptoms. Such an injury may be slow to heal in a patient with LPR, and make the patient aware of what had previously been clinically silent LPR. In these situations, it is important to rule out an underlying vocal fold mucosal injury or paresis with a careful evaluation often including laryngeal electromyography. The LPR patients who do not symptomatically improve with antireflux therapy often have another underlying laryngeal disorder such as a vocal fold paresis. Laryngeal examination reveals subtle bowing or hypomobility of one or both vocal folds. If the paresis fails to improve with time, treatment involves augmentation with injection laryngoplasty or medialization laryngoplasty. In some patients, pH probe testing while on antireflux medications is warranted to confirm an appropriate response to medication.Table 2: The reflux symptom index (RSI): a score greater than 5 in the proper clinical situation is strongly suggestive of laryngopharyngeal reflux (LPR) Full size tableTop of page Physical FindingsAlthough LPR has been associated with multiple otolaryngologic disorders, the most common physical findings of LPR are related to laryngeal mucosal edema and injury. Laryngeal mucosal injury can result in serious pathology ranging from ulcerative disease, granulomas, subglottic stenosis, and possibly laryngopharyngeal cancer. However, the most common findings during laryngoscopy are related to chronic inflammatory changes. The first such finding is pseudosulcus vocalis, which refers to infraglottic edema that passes posterior to the vocal process of the arytenoid cartilage (and can thereby be differentiated from true sulcus vocalis) (Figure 2). As an independent finding, pseudosulcus has been strongly associated with LPR.19, 20, 21 The second principal finding in LPR is ventricular obliteration, which refers to edema of the true and false vocal folds appearing to obliterate or obscure visualization of the laryngeal ventricle (Figure 3a), in contrast with the wide open laryngeal ventricles seen in Figure 3b. Interarytenoid and laryngeal erythema is also an LPR finding. However, erythema can vary greatly based on the light source, endoscope, and video monitor used, so this finding alone tends to hold less importance. True vocal fold edema is another important finding with LPR, which can vary from mild to severe polypoid degeneration. Figure 4 demonstrates such severe edema in a patient undergoing surgical voice rehabilitation. In addition to true vocal fold edema, diffuse laryngeal edema and posterior commissure hypertrophy are also common findings in LPR (Figure 5). Granulation tissue or granuloma formation may also be present.Figure 2:Infraglottic edema: a finding highly sensitive but not specific for laryngopharyngeal reflux (LPR).(Source: Belafsky et al.19, with permission from Lippincott, Williams and Wilkins.) Full size image (47 KB) Download Power Point slide (1,394 KB) Figure 3:a: Ventricular obliteration is secondary to edema of the true vocal folds and false vocal cords.b: Wide-open laryngeal ventricles in a patient who also has mild presbylaryngia. Full size image (19 KB) Download Power Point slide (780 KB) Figure 4:Intraoperative photo of polypoid degenerations of the true vocal folds (Reinkes edema). Full size image (79 KB) Download Power Point slide (2,056 KB) Figure 5:An extraordinary degree of diffuse laryngeal edema is seen in an individual with more than 80 episodes of LPR on pH testing. Full size image (47 KB) Download Power Point slide (1,952 KB) Analogous to the RSI, these laryngeal findings have been used to create the reflux finding score (RFS), which is a validated tool for LPR19 (Table 3). Although the RSI and RFS are not diagnostic for LPR and are not a replacement for pH monitoring, they do assist greatly in the diagnosis of LPR and in following the patients clinical response to treatment.Table 3: The reflux finding score (RFS): a score greater than 11 in the proper clinical situation is strongly suggestive of laryngopharyngeal reflux (LPR) Full size tableTop of page Laboratory FindingsDiagnostic modalities such as barium esophagography, radionucleotide scanning, and the Bernstein acid perfusion test have all been shown to have a low sensitivity and therefore have been largely abandoned as diagnostic tests for LPR. Recently, impedance monitoring has been introduced as a modality that allows detection of both acidic and nonacidic reflux events. Impedance may play a role in detecting nonacidic reflux events in symptomatic patients who have had negative pH probe studies, or in LPR patients who are refractory to antireflux therapy. Its most significant role may be in the evaluation of pulmonary patients such as those with chronic cough and refractory reactive airways diseases and chronic obstructive pulmonary disease (COPD). However, because of the newness of the technology, there is currently little information available on the application of impedance testing to LPR patients. Although dual pH probe monitoring has several disadvantages, with the greatest being patient discomfort, it remains the most sensitive and specific diagnostic test available for LPR.22, 23Dual pH probe testing is typically done in an outpatient setting with the patient being monitored over a 18- to 24-hour period. Using manometry, or endoscopic guidance, the lower probe is placed approximately 5 cm above the lower esophageal sphincter, with the upper probe placed just above the UES. This placement of the upper or proximal probe is essential, because the UES functions as the final barrier against LPR. Thus, proximal esophageal reflux does not accurately reflect extraesophageal or pharyngeal reflux events owing to the protective function of the UES.24, 25The pH probe