The GERD, The Bed, & The Ugly

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Nocturnal GERD may be more important than daytime GERD in the development of severe GERD-related complications; and up to 80% of refluxers describe nocturnal symptoms. Nighttime reflux is associated …

Nocturnal GERD may be more important than daytime GERD in the development of severe GERD-related complications; and up to 80% of refluxers describe nocturnal symptoms. Nighttime reflux is associated with a 11x risk of esophageal adenocarcinoma, as well as sleep disturbance and respiratory symptoms.
Perhaps you don’t need to know the details of nocturnal GERD… but ask yourself-
“Do you feel lucky?”

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  • Speaker Notes : This program is designed to answer the following questions: Why is nighttime a special period of risk for reflux complications? What symptoms are linked to nighttime reflux? What areas should be explored to effectively diagnose nighttime reflux? How should nighttime reflux be managed?
  • Speaker Notes : A 66-year-old man reports for a first time visit to a new primary care physician. He retired to Florida 2 months ago and is complaining of excessive daytime sleepiness. Previous medical history includes hypertension and hypercholesterolemia. His current medications are hydrochlorothiazide and pravastatin. Physical exam reveals a 6'0'' man weighing 96 kg. His blood pressure is relatively well controlled at 140/90 mm Hg. His level of sleepiness on the Epworth Sleepiness Scale is 11, which indicates daytime sleepiness. 1 The physician decides to gather more information to rule out sleep apnea or other sleep disorders. The physician encourages the patient to try lifestyle modification for several weeks and instructs him to reduce late-night caffeine intake and to increase the daytime activity level. 2 The physician also suggests that he keep a sleep log of the time it takes him to fall asleep, how he sleeps, and how he feels when he wakes up and also asks him to query his wife to see if she notices anything while he sleeps (i.e., loud snoring or choking, which would be consistent with sleep apnea). 2 References : 1. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–545. 2. Czeisler CA, Richardson GS. Detection and assessment of insomnia. Clin Ther. 1991;13:663–679.
  • Speaker Notes : The patient returns 3 weeks later with a sleep log and his wife. Despite adopting the suggested lifestyle modifications, he reports that he is still very sleepy during the day. His wife reports that she is not awakened by any snoring or choking episodes. She does, however, note that he frequently coughs throughout the night. She reports that he wakes up during these coughing spells, but the patient does not recall these spells. For his part, the patient only remembers awakening feeling unrefreshed a couple of times per week, with occasional morning hoarseness. Upon further questioning, the patient reports that when he lies down to sleep, he sometimes has bouts of epigastric discomfort that radiate upward toward the throat and back toward the spine. He has experienced this feeling before when he was traveling on business, and he self-medicated successfully with antacids. However, he no longer achieves relief with antacids. Based on the presentation of heartburn, nighttime cough, and a history of self-medication, the physician has reached a preliminary diagnosis of GERD, specifically nighttime reflux. This case is consistent with other reports (to be further discussed in this presentation), that nighttime gastroesophageal reflux causes sleep disturbance that may manifest as excessive daytime sleepiness. 1,2 References : 1. Konermann M, Sanner B, Kopp H, Burmann-Urbanek M. Nocturnal gastroesophageal reflux in hypersomnic patients without sleep related breathing disorder. Somnologie. 1998;2:3–7. 2. Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–163.
  • References : 1. Orr WC, Johnson LF, Robinson MG. Effect of sleep on swallowing, esophageal peristalsis, and acid clearance. Gastroenterology. 1984;86:814–819. 2. Orr WC, Robinson MG, Johnson LF. Acid clearance during sleep in the pathogenesis of reflux esophagitis. Dig Dis Sci . 1981;26:423–427. 3. Kjellén G, Tibbling L. Influence of body position, dry and water swallows, smoking, and alcohol on esophageal acid clearing. Scand J Gastroenterol. 1978;13:283–288. 4. Orr WC, Elsenbruch S, Harnish MJ, Johnson LF. Proximal migration of esophageal acid perfusions during waking and sleep. Am J Gastroenterol. 2000;95:37–42. Speaker Notes : Sleep poses a period of risk for reflux-related complications because the protective mechanisms to clear reflux are attenuated or eliminated. Under waking conditions, protective mechanisms to clear reflux include gravity, peristalsis, salivation, and intrinsic mucosal defense mechanisms. In a study by Orr using asymptomatic healthy subjects, infusion of acid into the esophagus increased swallowing frequency and decreased esophageal clearance time in comparison with results of water infusion as a control. However, during sleep these responses were markedly reduced, with decreased swallowing and prolonged esophageal clearance. 1 An earlier study demonstrated prolonged clearance of infused acid during sleep in both asymptomatic healthy controls and patients with at least daily heartburn and esophagitis seen on endoscopy (including erythema, friability, and ulcerations). 2 Gravitational forces that normally act to clear refluxate are also attenuated in the supine position. 3 These changes in the normal defenses against reflux can result in proximal migration of infused acid and prolonged mucosal contact time. 4
  • References : 1. Freidin N, Fisher MJ, Taylor W, et al. Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. Gut. 1991;32:1275–1279. 2. Orr WC, Allen ML, Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage. Am J Gastroenterol. 1994;89:509–512. 3. Johnson LF, DeMeester TR. Development of the 24-hour intraesophageal pH monitoring composite scoring system. J Clin Gastroenterol. 1986;8(suppl 1):52–58. Speaker Notes : Upright reflux events are frequent but short; recumbent reflux events tend to be less frequent but can be prolonged. The propensity for upright reflux and recumbent reflux varies among patients, and when reflux events occur, they have different patterns. In general, upright reflux events occur more frequently than do recumbent reflux events. 1 As shown in the graphic, upright reflux episodes also tend to be shorter in duration than recumbent reflux events, which can be prolonged. 2,3
  • Nighttime heartburn is common. In 2000, the Gallup Organization, in conjunction with the American Gastroenterological Association, conducted a large telephone survey of 1,000 adult respondents who suffer from heartburn at least weekly. When these respondents were questioned about whether they experienced nighttime heartburn, 79% of patients who experienced weekly heartburn reported experiencing nighttime heartburn. 1 Farup and colleagues conducted another large population telephone survey. They found that, of 1,284 adults surveyed who had GERD symptoms at least once a week, 74% (n=945) reported experiencing nighttime heartburn. 2 These findings surprised the gastroenterology community. Nighttime heartburn was not recognized as a major problem with substantial consequences. References : 1. Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an underappreciated clinical problem that impacts sleep and daytime function. Gastroenterology. 2001;120(Suppl 1):A-433. 2. Farup C, Kleinman L, Sloan S, et al. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med. 2001;161:45–52. Speaker Notes :
  • Reference : 1. Farup C, Kleinman L, Sloan S, et al. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med. 2001;161:45–52. Speaker Notes : In this survey, patients with nighttime GERD reported a poorer health status compared with the general U.S. population and daytime GERD patients. Nighttime GERD impairs the patient’s health status. In a phone survey that examined the impact of nighttime GERD on general health status, quality-of-life (QOL) scores for U.S. population norms and patients with daytime GERD were used as comparators. 1 The Farup study was a survey of 1,284 respondents who had heartburn and/or regurgitation at least once a week. Of these respondents, 945 reported significant nighttime GERD symptoms in the last 3 months. To assess general health status, Farup and colleagues used the Medical Outcomes Study Short-Form 36 Health Survey (SF-36), which measures QOL in several domains of function. As shown in the graph, scores in the domains of bodily pain, general health, vitality, social functioning, mental health, and role limitations-emotional were all significantly lower in patients experiencing nighttime GERD when compared with the control population. When compared with patients with daytime GERD, nighttime GERD patients had significantly lower scores in all measured domains. 1
  • References : 1. Orr WC, Allen ML, Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage. Am J Gastroenterol. 1994;89:509–512. 2. Adachi K, Fujishiro H, Katsube T, et al. Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis. J Gastroenterol Hepatol. 2001;16:1191–1196. 3. DeMeester TR, Johnson LF, Joseph GJ, et al. Patterns of gastroesophageal reflux in health and disease. Ann Surg. 1976;184:459–470. Speaker Notes : Patients with erosive GERD have more prolonged periods of recumbent reflux than patients with nonerosive GERD. Several studies have found links to more severe forms of erosive GERD in patients with supine reflux. Orr and colleagues studied the ability to clear refluxate in 54 patients who were endoscopically identified as nonerosive (either normal or erythema, friability; n=21) or erosive (erosions/ulcerations including Barrett’s esophagus; n=33). 1 As shown in the graph, they found that patients with erosive GERD had more frequent episodes of reflux while in the recumbent position as well as more recumbent episodes of >5 minutes than did patients with nonerosive GERD. Indeed, upon stepwise discriminant analysis, the number of recumbent reflux episodes >5 minutes in duration was the most significant factor at variance between the 2 groups. 1 For comparison, during the upright period, the number of reflux episodes per hour was higher in erosive vs. nonerosive GERD patients (8.7 vs. 5.3; P <0.05); and the number of recumbent episodes >5 min per hour was numerically higher in erosive vs. nonerosive patients (0.28 vs. 0.14; P =ns). Adachi and colleagues studied 37 patients (in Japan) with erosive GERD (as determined by the Los Angeles Classification system) and compared them with 20 patients who had no esophagitis. They found that gastroesophageal reflux occurred more frequently in patients with high-grade erosive GERD and that patients with grades C and D esophagitis had prolonged nighttime esophageal refluxate exposure. 2 In an early study, DeMeester and colleagues compared the distribution of patients with esophagitis while in the supine position against those whose esophagitis resulted from reflux while upright. One hundred patients with heartburn and regurgitation and abnormal 24-hr esophageal pH were compared with 15 who had no reflux history. They found statistically more patients with esophagitis in the supine reflux group vs. the upright reflux group. 3
  • References : 1. Robertson D, Aldersley M, Shepherd H, Smith CL. Patterns of acid reflux in complicated oesophagitis. Gut. 1987;28:1484–1488. 2. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340:825–831. 3. DeVault KR, Castell DO, and The Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:1434–1442. 4. Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–163. 5. Understanding Heartburn in America . Princeton, NJ: The Gallup Organization; 2000:1-40. 6. el-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology . 1997;113:755–760. Speaker Notes : Complications of GERD can be divided into those related to esophageal disease progression and those related to atypical manifestations, many of which are linked to supine position or nighttime reflux. GERD can progress to erosive esophagitis, with a small proportion of patients developing additional complications such as adenocarcinoma. Stages along this esophageal disease progression include erosions, ulceration, strictures, Barrett’s esophagus, and adenocarcinoma. Nighttime reflux has been linked with more severe forms of erosive esophagitis (which include ulcerations, strictures, and Barrett’s esophagus). 1 Nighttime symptoms may also increase the risk of cancer. A nationwide population-based, case-controlled study conducted in Sweden found that patients who had nighttime heartburn and/or regurgitation at least once a week were nearly 11 times more likely to develop adenocarcinoma of the esophagus than were the asymptomatic controls (OR 10.8; 95% CI, 7.0–16.7). 2 For comparison, patients with heartburn and/or regurgitation at least once a week (day or night) had an eightfold increase in esophageal adenocarcinoma. Atypical complications are also common in GERD patients. Although some patients with nighttime GERD will present with the typical symptoms of GERD (heartburn or regurgitation), 3 others may present more subtly. These subtle presentations may mask GERD. Patients with symptoms of nighttime GERD may experience sleep disturbances that can be measured objectively, or they may experience reduced functionality the next day related to sleep deprivation. 4,5 Respiratory disturbances that are increased in frequency in patients with nighttime GERD include asthma and chronic cough. 3,4,6
  • The symptom constellation associated with nighttime reflux often differs from that associated with daytime reflux. GERD is a 24-hour disease, with the majority of patients experiencing both daytime and nighttime symptoms. 1 However, the symptoms associated with daytime and nighttime reflux events may differ. Heartburn and regurgitation are common symptoms that happen during the day in GERD patients, often postprandially. 2 However, as has been discussed, the experience of heartburn and regurgitation can be different at night—heartburn might be absent and regurgitation can lead to coughing. 3 The study by Gislason et al was conducted in Europe and identified patients with nocturnal GERD by the presence of heartburn or belching after going to bed at least once a week. Sleep disturbance, which can cause daytime sleepiness, can be a manifestation of nighttime reflux. 3 Note that daytime sleepiness is one symptom that shows the lingering effects of nighttime reflux during the following day. Reflux reported to occur after bedtime is strongly associated with a high prevalence of asthma and respiratory symptoms. 3 References : 1. Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an underappreciated clinical problem that impacts sleep and daytime function. Gastroenterology. 2001;120(Suppl 1):A-433. 2. DeVault KR, Castell DO, and The Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:1434–1442. 3. Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–163. Speaker Notes :
  • At night, heartburn may not have the typical presentation or may not be reported. The classic symptoms of GERD include regurgitation and heartburn (i.e., a retrosternal burning sensation that radiates upward toward the neck). Heartburn has a high specificity and sensitivity for GERD. However, the actual symptoms with which GERD may present are variable. One of the points of differentiation is that the pain of GERD is usually episodic, not continuous. 1 The sleeping patient may have a diminished awareness of heartburn. 2 Even if patients experience heartburn during sleep, they may not recall it. Not all patients will recognize heartburn, even when awake. Patients have variable pain thresholds, so not all patients will report heartburn from the same degree of esophageal damage. There may be cultural differences in this response. Finally, extraesophageal manifestations of GERD, such as asthma, cough, hoarseness, and throat clearing, frequently present without heartburn. 3,4 So if one is relying on the presence of heartburn as a defining symptom, atypical reflux might be missed. Clinical pearl: Don’t rely on heartburn alone to diagnose nighttime GERD. References : 1. New Considerations in the Evaluation and Management of Gastroesophageal Reflux Disease (GERD) . Chicago, Ill: American Medical Association; 2002. 2. Orr WC. Arousals from sleep: is a good night's sleep really good? Int J Neurosci. 1980;11:143–144. 3. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991;101:1–78. 4. Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med . 2000;162:34–39. Speaker Notes :
  • References : 1. Understanding Heartburn in America . Princeton, NJ: The Gallup Organization; 2000:1-40. 2. Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–163. 3. Farup C, Kleinman L, Sloan S, et al. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med. 2001;161:45–52. Speaker Notes : Nighttime GERD impairs sleep and may affect next-day function. In a Gallup survey, 1,000 respondents with weekly heartburn were asked about the impact of heartburn on sleep. Sixty-three percent reported that heartburn affects sleep, 56% reported an effect on their ability to sleep when they wanted, and 40% reported that heartburn affected their ability to function well at work the next day. 1 Gislason and colleagues 2 conducted a large population study (in Ireland, Belgium, and Sweden) in which they stratified patients based on presence of nighttime GERD symptoms (n=101) vs. no nighttime GERD symptoms (n=2,096). Patients who reported heartburn or belching when going to bed at least 1 to 2 nights per week were assigned to the nighttime gastroesophageal reflux group. 2 As shown in the slide, they found that patients with nighttime GERD were more likely to experience snoring, apnea, nightmares, and daytime sleepiness than patients without nighttime GERD (controls). The Farup study was a survey of 1,284 respondents who had heartburn and/or regurgitation at least once a week. Of these respondents, 945 reported nighttime GERD symptoms in the last 3 months. 3 This study also documented nighttime sleep disturbances in some patients experiencing nighttime GERD symptoms. The most common nighttime complaints were experiencing GERD symptoms when laying down to sleep at night (69%), awakening at night due to GERD symptoms (54%), experiencing GERD symptoms upon awakening in the morning (40%), and awakening at night due to coughing or choking because of fluid, an acid/bitter taste, or food in the throat (29%).
  • Reference : 1. Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–163. Speaker Notes : Nighttime GERD is associated with respiratory disturbances. Gislason and colleagues, in a European study involving 2,661 subjects, examined the relationship between nighttime GERD symptoms and respiratory disturbances. Patients who reported heartburn or belching when going to bed 1 to 2 nights per week were assigned to the nighttime gastroesophageal reflux group. 1 As shown in the table, the adjusted odds ratios for symptoms such as wheeze, nighttime chest tightness, nighttime breathlessness, asthma, and nighttime cough were >2 times greater in the nighttime GERD group (n=101) compared to the subjects without nighttime GERD (n=2,096). 1
  • At night, regurgitation may manifest as coughing and choking. Regurgitation, the effortless return of gastric contents into the pharynx, is considered one of the hallmarks of GERD. 1 However, this symptom may present differently at night. Since airway protective mechanisms are active at night, regurgitation may manifest as choking. The classic definition of regurgitation is the presentation of a sour taste in the mouth. However, it may be nonacidic. 2 The clinician should query the patients about regurgitation symptoms. These include: Do you taste something in your mouth? Does it make you cough or choke? Does it make you lose your breath? References : 1. Szarka LA, Locke GR. Practical pointers for grappling with GERD. Heartburn gnaws at quality of life for many patients. Postgrad Med. 1999;105:88–105. 2. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991;101:1–78. Speaker Notes :
  • Patients with nighttime reflux that reaches the upper esophageal sphincter are at increased risk of aspiration, as indicated by increased nighttime cough and increased supine acid contact time. Tomonaga and colleagues conducted a study to determine if any symptoms of GERD are predictive of aspiration risk. They performed ambulatory dual-probe esophageal pH monitoring in 133 patients with upper airway disturbances and additional symptoms for GERD. Using two glass probes, both distal and proximal sensors were placed 5 cm above the proximal border of the LES and 1 cm below the lower border of the upper esophageal sphincter. 1 Patients who were positive at the proximal port had increased nocturnal cough and increased supine acid contact time compared with the patients in the other groups. 1 These results show that patients with nighttime reflux that reaches proximal portions of the esophagus are at increased risk of nighttime cough, a marker of aspiration potential. Reference : 1. Tomonaga T, Awad ZT, Filipi CJ, et al. Symptom predictability of reflux-induced respiratory disease. Dig Dis Sci . 2002;47:9–14. Speaker Notes :
  • Speaker Notes : A 28-year-old man presents complaining of chronic cough. He is wheezing daily. His previous medical history reveals onset of mild asthma 1 year ago. He is currently taking inhaled albuterol as needed. His physical examination reveals wheezing but is otherwise unremarkable. His pulmonary function tests show forced expiratory volume in 1 second is 70% of predicted. Additionally, the FEV 1 /FVC ratio is less than 0.70%. This indicates small airflow obstruction. Peak flow variability is >30%. The physician tells the patient that his asthma has progressed (it is now moderate persistent asthma). Therapy is changed to inhaled flunisolide and salmeterol (for nighttime symptoms). The patient is instructed to continue use of inhaled albuterol as needed. 1 Reference : 1. National Institutes of Health. National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. 1997. NIH Publication 97-4051.
  • Speaker Notes : The patient returns for a follow-up visit 3 months later. He reports that his symptoms are unchanged; physical exam and PFTs confirm this. The physician questions the patient further and examines the patient in supine and upright positions. He has a high suspicion of nighttime reflux contributing to the asthma exacerbations for the following reasons 1 : adult onset; wheezing worsened by supine position; nighttime cough; and heartburn 2 times per week, at night. The physician diagnoses the patient with nighttime GERD. Reference : 1. New Considerations in the Evaluation and Management of Gastroesophageal Reflux Disease (GERD ). [Pamphlet]. Chicago: AMA; 2002.
  • Asthma may be related to GERD through micro-aspiration (reflux) or a neurally-mediated reflex causing bronchospasm. The association between gastroesophageal reflux disease and pulmonary disorders has been studied extensively. These pulmonary disorders include asthma, chronic cough, pulmonary fibrosis, chronic bronchitis, laryngitis, and bronchiectasis. 1 Two basic theories have been proposed to explain how gastroesophageal reflux could relate to asthma. These are shown in the graphic. The first theory is the reflux (or aspiration) theory. This theory proposes that microaspiration of gastric contents into the lung leads to bronchoconstriction. The second theory, called the reflex (or vagal) theory, proposes that GERD-related stimulation of acid-sensitive receptors in the esophagus leads to wheezing via vagal neural pathways that trigger bronchoconstriction. 2 In addition, the causality can be inverted. Not only can GERD induce asthma, asthma can induce GERD. Many of the asthma medications used to alleviate bronchoconstriction decrease lower esophageal sphincter pressure. 3 References : 1. Gonvers JJ, Zellweger JP, Leuenbergher P, Fraser R. Asthma, respiratory disease and gastro-oesophageal reflux. Gullet. 1993;3(suppl):53–59. 2. Barish CF, Wu WC, Castell DO. Respiratory complications of gastroesophageal reflux. Arch Intern Med . 1985;145:1882–1888. 3. Harding SM. Acid reflux and asthma. Curr Opin Pulm Med. 2003;9:42–45. Speaker Notes :
  • The goals of therapy for nighttime GERD are to eliminate symptoms, heal esophagitis, and improve sleep. The goals for managing nighttime GERD do not differ from those of any GERD patient: eliminate symptoms and promote healing (if esophagitis is present). This approach should help prevent the development of complications. 1 In the case of nighttime GERD, an additional goal is to improve sleep, because nighttime GERD can lead to sleep disturbances. The Gallup poll revealed that many patients with nighttime heartburn are not satisfied with their current therapy. Of the patients with nighttime heartburn, 53% reported that they would try anything to relieve symptoms. 2 Approximately 45% of these nighttime heartburn patients report that the current remedies do not relieve all symptoms. 2 References : 1. New Considerations in the Evaluation and Management of Gastroesophageal Reflux Disease (GERD) . Chicago, Ill: American Medical Association; 2002. 2. Understanding Heartburn in America . Princeton, NJ: The Gallup Organization; 2000:1–40. Speaker Notes :
  • The goals of therapy for nighttime GERD are to eliminate symptoms, heal esophagitis, and improve sleep. The goals for managing nighttime GERD do not differ from those of any GERD patient: eliminate symptoms and promote healing (if esophagitis is present). This approach should help prevent the development of complications. 1 In the case of nighttime GERD, an additional goal is to improve sleep, because nighttime GERD can lead to sleep disturbances. The Gallup poll revealed that many patients with nighttime heartburn are not satisfied with their current therapy. Of the patients with nighttime heartburn, 53% reported that they would try anything to relieve symptoms. 2 Approximately 45% of these nighttime heartburn patients report that the current remedies do not relieve all symptoms. 2 References : 1. New Considerations in the Evaluation and Management of Gastroesophageal Reflux Disease (GERD) . Chicago, Ill: American Medical Association; 2002. 2. Understanding Heartburn in America . Princeton, NJ: The Gallup Organization; 2000:1–40. Speaker Notes :
  • Gastroenterologists recommend that patients adopt lifestyle modifications such as bed elevation, avoidance of meals immediately before going to bed, etc., to manage nighttime gastroesophageal reflux. However, the benefits of such approaches have not been established in clinical trials. 1 OTC medications can be useful for relief of mild heartburn. Prescription medications can show excellent efficacy for the management of nighttime GERD symptoms such as heartburn and regurgitation. 2 References : 1. DeVault KR, Castell DO, and The Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:1434–1442. 2. Richter JE, Bochenek W, and the Pantoprazole US GERD Study Group. Oral pantoprazole for erosive esophagitis: a placebo-controlled, randomized clinical trial. Am J Gastroenterol. 2000:95:3071–3080. Speaker Notes :
  • Speaker Notes : Physicians need to ask key questions about heartburn, regurgitation, extraesophageal manifestations, and sleep to assess whether patients have nighttime GERD. Because patients do not always report nighttime GERD symptoms, physicians need to actively question patients about GERD symptoms. Some leading experts in nighttime GERD recommend that you ask patients about the following issues to assess nighttime GERD: Symptoms of heartburn, regurgitation, chronic cough, chronic hoarseness, difficulty breathing, wheezing, or frequent throat clearing Effect of position on symptom (recumbency vs. upright) Effect of symptom(s) on sleep (falling asleep, staying asleep, waking refreshed) History and efficacy of the patient’s symptom management
  • Hopefully, this presentation has helped you develop answers to the questions we posed at the beginning of the program: Why is nighttime a period of risk for reflux complications? Protective mechanisms reduced/absent = prolonged esophageal exposure to refluxate Which symptoms are linked to nighttime reflux? Nighttime asthma/cough, sleep disturbance, etc. Which areas should be explored to effectively diagnose nighttime reflux? Effect on sleep, dependency on position, patient management strategies How should nighttime reflux be managed? Acid suppression, possibly lifestyle modification Speaker Notes :

Transcript

  • 1. RxForSanity.com Visit today for a FREE subscription to our eZine, with monthly medical humor and new educational presentations! www.RxForSanity.com
  • 2. The GERD, The Bed, & the Ugly: Nighttime Gastroesophageal Reflux www.RxForSanity.com Patricia L. Raymond MD FACG Rx For Sanity
  • 3. Evolving Concepts of Nighttime Reflux
    • Why is nighttime a special period of risk for reflux complications?
    • What symptoms are linked to nighttime reflux?
    • What areas should be explored to effectively diagnose nighttime reflux?
    • How should nighttime reflux be managed?
    www.RxForSanity.com
  • 4. Nothing wrong with shooting as long as the right people get shot. Magnum Force 1973 www.RxForSanity.com
  • 5. What is GERD? “ GERD is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications” Montr é al definition of GERD Vakil et al. Am J Gastroenterol 2006;101:1900–20
  • 6. The Montréal definition of GERD “ GERD is a condition which develops when the reflux of stomach content causes troublesome symptoms and/or complications” Esophageal Syndromes Extra-esophageal Syndromes Symptomatic Syndromes
    • Typical Reflux Syndrome
    • Reflux Chest Pain Syndrome
    Syndromes with Esophageal Injury
    • Reflux Esophagitis
    • Reflux Stricture
    • Barrett’s Esophagus
    • Adenocarcinoma
    Established Associations
    • Reflux Cough
    • Reflux Laryngitis
    • Reflux Asthma
    • Reflux Dental Eros.
    Proposed Associations
    • Pharyngitis
    • Sinusitis
    • Idiopathic Pulmonary Fibrosis
    • Recurrent Otitis Media
    Vakil et al. Am J Gastroenterol 2006;101:1900–20
  • 7. The prevalence of GERD is increasing Non-white men White men White women Non-white women Death rate per million Proportional rate per 10,000 hospitalisations 0.0 0.5 1. 0 1.5 2. 0 2.5 0 100 200 250 350 400 50 150 300 Reflux esophagitis (year) GERD (year) 1968– 1972 1973– 1977 1978– 1982 1983– 1987 1988– 1992 1970– 1974 1975– 1979 1980– 1984 1985– 1989 1990– 1992 El-Serag & Sonnenberg. Gut 1998;73:327–33
  • 8. The prevalence of GERD is underestimated – many individuals do not consult a physician Consulted a physician Consulted a pharmacist Used antacids Heartburn sufferers (%) 0 20 4 0 60 8 0 100 n=568 Louis et al. Eur J Gastroenterol Hepatol 2002;14:279–84
  • 9. GERD is common at all ages Prevalence (%) 0 2 0 40 6 0 80 25–34 35–44 45–54 55–64 65–74 Age (years) At least weekly episodes of GERD symptoms Females Males Locke et al. Gastroenterology 1997;112:1448–56
  • 10. Frequency and severity of heartburn in antacid users who have not consulted a physician Daily Several times per week Mild Frequent antacid users (%) 0 20 4 0 60 8 0 100 n=155 Moderate Severe Heartburn frequency Heartburn severity Robinson et al. Arch Intern Med 1998;158:2373–6
  • 11. Reflux esophagitis or GERD complications in antacid users who have not consulted a physician Wheezing Odynophagia Hoarseness Dysphagia Barrett’s esophagus (non-dysplastic) Reflux esophagitis 0 20 40 60 80 100 Frequent antacid users (%) n=155 Robinson et al. Arch Intern Med 1998;158:2373–6
  • 12. Quality of life of patients with GERD is impaired compared with the general population Patients with GERD Mean HRQL score (SF-36) 0 20 40 60 80 100 Physical functioning Role physical Bodily pain General health Vitality Social functioning Role emotional Mental health German normative population Kulig et al. Aliment Pharmacol Ther 2003;18:767–76
  • 13. Heartburn affects many aspects of everyday life in adults with GERD Individuals with activity affected (%) n>130,000 0 20 40 60 80 100 Liker et al. J Am Board Fam Pract 2005;18:393–400 Enjoying food Eating out Sleep Work Family activities Exercise Socialising Travel for pleasure Intimacy/sex Gardening Time with spouse Business Hobbies Playing with kids Team sports
  • 14. Quality of life deteriorates as the severity of reflux symptoms increases Wiklund et al. Am J Gastroenterol 2006;101:18–28 Heartburn severity (GSRS score) General population of Malm ö , Sweden n=1476 PGWB, Psychological General Well Being GSRS, Gastrointestinal Symptom Rating Scale None Very severe Well-being (PGWB score) 0 20 40 100 140 1 2 3 4 5 6 7 60 80 120 Healthy individuals Clinically meaningful impairment of well being
  • 15. There's plain few problems can't be solved with a little sweat and hard work. Pale Rider 1985 www.RxForSanity.com
  • 16. Economic impact related to symptom severity Moderate heartburn Severe heartburn No heartburn Mild heartburn Mean duration of absence from work per week (hours) 0 2 4 6 8 1 3 5 7 Reduction in productivity at work ( %) 0 10 20 25 35 5 15 30 Reduction in productivity during regular daily activities (%) 0 20 40 50 60 10 30 Wahlqvist et al. Value Health 2002;5:106–13
  • 17. Reduction in work productivity due to GERD is comparable to that for other chronic diseases Productivity loss (hours/week) 5.7 6.1 5.7 4.8 4.1 3.3 1.0 0.7 1.3 0.6 0.6 1.1 0 2 4 6 8 10 GERD n=273 Back pain n=125 Headache n=129 Arthritis n=124 Allergies n=292 High blood pressure n=129 Present at work Absent from work Adapted from Dean et al. Gastroenterology 2003;124(Suppl 1):A505
  • 18. Case Study: Excessive Daytime Sleepiness
    • 66-y.o. man, recently retired, c/o daytime sleepiness
    • PMHx: Hypertension, hypercholesterolemia
    • Current meds: Hydrochlorothiazide, pravastatin
    • PE: 6 ' 0 '' , 96 kg; BP: 140/90 mm Hg;  daytime sleepiness
    • R/o: Sleep apnea, other sleep disorders
    • Prescribed lifestyle modifications: Reduce caffeine intake; increase daytime activity
    • Keep sleep log (including spouse report)
    www.RxForSanity.com
  • 19. Case Study: Return Visit at 3 Weeks
    • Adopted lifestyle modifications
    • Still very sleepy during the day
    • Sleep log
      • No snoring/choking episodes
      • Frequent nighttime cough (spouse aware, patient not)
      • Awakes unrefreshed, some morning hoarseness
    • Further questioning
      • Occasional epigastric discomfort, radiating toward throat/spine
      • Previous self-medication with antacids
    www.RxForSanity.com
  • 20. Supine Position/Sleep Diminish Protective Barriers Against GE Reflux www.RxForSanity.com  Esophageal acid clearance 1–3 1 Orr W, et al. Gastroenterology. 1984;86:814–819. 2 Orr W, et al. Am J Gastroenterol. 2000;95:37–42. 3 Orr W, et al. Am J Gastroenterol. 1994;89:509–512. 4 Kjell én G, Tibbling L. Scand J Gastroenterol . 1978;13:283–288.  Salivary flow and swallowing 1  Gravity-mediated drainage 4
  • 21. Recumbent Reflux Events Can Be Prolonged www.RxForSanity.com * = Patient reported heartburn Courtesy of William C. Orr, PhD Esophageal pH Daytime (Upright) Reflux (GERD Patient) Nighttime (Recumbent) Reflux (GERD Patient) Elapsed Recumbent Time Elapsed Upright Time 8 6 4 2 0 1 hr 2 hr 2 hr Esophageal pH 8 6 4 2 0 1 hr * * *
  • 22. Nighttime Heartburn: Prevalent in People With Heartburn www.RxForSanity.com Those Reporting Nighttime Heartburn 1 Shaker R, et al. Gastroenterology . 2001;120(Suppl 1):A-433. 2 Farup C, et al. Arch Intern Med . 2001;161:45–52. 74% 79% N=1,000 adults with heartburn at least once a week N=1,284 adults with GERD symptoms at least once a week AGA Survey 1 Farup et al. 2
  • 23. Nighttime GERD Reduces Health Status Even More Than Daytime GERD www.RxForSanity.com N=1,552 SF-36=Medical Outcomes Study Short-Form 36 Health Survey * P <0.001 vs. control group for all scales except “Physical Functioning.” P <0.001 vs. daytime GERD for all scales. Adapted from Farup C, et al. Arch Intern Med . 2001;161:45–52. 30 50 70 90 Nighttime GERD* Daytime GERD Control Group Physical Functioning Role Limitations–Physical Bodily Pain General Health Vitality Social Functioning Role Limitations– Emotional Mental Health SF-36 Score (n=945) (n=339) (n=268) Worse Better
  • 24. Recumbent Reflux Episodes Are More Frequent and Prolonged in Erosive GERD Patients www.RxForSanity.com * * * P <0.05 vs. nonerosive esophagitis patients Adapted from Orr WC, et al. Am J Gastroenterol . 1994;89:509–512. Recumbent Reflux Episodes Prolonged (>5 min) Recumbent Reflux Episodes 0 1 2 3 4 5 Nonerosive (n=21) Erosive (n=33) Number/Hr (mean) 0 0.1 0.2 0.3 0.4 0.5 Nonerosive (n=21) Erosive (n=33) Number/Hr (mean) Results of Ambulatory pH Monitoring
  • 25. Nighttime Reflux Increases Risks of GERD Complications
    • Erosive esophagitis 1
    • Complicated erosive esophagitis 2
      • Ulceration
      • Strictures
      • Barrett’s esophagus
    • Adenocarcinoma 3
    • Sleep deprivation 4
    www.RxForSanity.com 1 Orr WC, et al. Am J Gastroenterol . 1994;89:509–512. 2 Robertson D, et al. Gut . 1987;28:1484–1488. 3 Lagergren J, et al. N Engl J Med . 1999;340:825–831. 4 Gislason T, et al. Chest. 2002;121:158–163. Esophageal Disease Progression Atypical Complications Other Symptoms Respiratory disturbances 4
  • 26. Common Symptoms Related to Daytime and Nighttime Reflux Events www.RxForSanity.com Symptoms reliably reported on by patients Symptoms masked by ‘sleep,’ resulting in less recall and reporting by patients * Symptom often experienced in daytime hours but results from nighttime reflux. 1 DeVault KR, et al. Am J Gastroenterol . 1999;94:1434–1442. 2 Gislason T, et al. Chest. 2002;121:158–163. Heartburn (variable) Sleep disturbance/daytime sleepiness* Coughing Wheezing 1 Nighttime Symptoms 1,2 Heartburn Regurgitation Wheezing Daytime Symptoms 1
  • 27. At Night, GERD Patients May Not Present With Heartburn
    • Typical daytime presentation
      • Retrosternal burning sensation, radiating upward toward the neck 1
        • High specificity and sensitivity
        • Others present with pressure, epigastric pain, etc.
      • Extraesophageal manifestations may present without heartburn 2
    • Nighttime manifestations
      • During sleep, heartburn may not be felt
      • If present, patients may not recall or report
        • Daytime heartburn may be absent
    • Clinical pearl: Don’t rely on heartburn alone to diagnose nighttime GERD.
    www.RxForSanity.com 1 New Considerations in the Evaluation and Management of Gastroesophageal Reflux Disease (GERD) . [Pamphlet]. Chicago: AMA; 2002. 2 Koufman JA. Laryngoscope . 1991;101:1–78.
  • 28. Nighttime GERD Implicated in Sleep Disturbances www.RxForSanity.com Adapted from Gislason T, et al. Chest. 2002;121:158–163. * P <0.001; † P <0.01; ‡ P <0.05 Symptom Controls: No Nighttime Reflux (n=2,096) Nighttime Reflux (n=101) Nighttime symptoms (%) Snoring ( > 3 nights/wk) 5 16* Reported apnea ( > 1 night/wk) 1 5 † Nightmares ( > 1 night/wk) 4 17* Daytime symptoms (%) Daytime sleepiness ( > 3 days/wk) 14 30* Involuntary falling asleep ( > 1 day/wk) 4 8 ‡
  • 29. Nighttime GERD and Associated Respiratory Disturbances www.RxForSanity.com Adapted from Gislason T, et al. Chest. 2002;121:158–163. * P <0.001; † P <0.05 Symptoms Controls: No Nighttime Reflux (n=2,096) (%) Nighttime Reflux (n=101) (%) Wheezing 24 47* Nighttime chest tightness 11 23* Nighttime breathlessness 4 13* Asthma 4 9 † Nighttime cough 31 59*
  • 30. Assessing Regurgitation in Nighttime Reflux
    • Regurgitation
      • Possibly related to volume
      • May present as sour taste in mouth, but not always
      • May be nonacid
    • Nighttime presentation
      • May manifest as coughing
      • Micro-aspiration
    • Clinical pearl: At night, regurgitation may manifest as coughing and choking.
    www.RxForSanity.com Koufman JA. Laryngoscope . 1991;101:1–78. Orr WC. Am J Gastroenterol . 2000;95:37–42.
  • 31. Nighttime Reflux May Increase Risk of Micro-aspiration www.RxForSanity.com Tomonaga T, et al. Dig Dis Sci. 2002;47:9–14.
    • 133 patients with airway disturbance and GERD
    • Proximal reflux episodes
      • Frequent in supine position
      • Correlated with nighttime cough
    Distal probe Proximal probe
  • 32. Case Study: Asthma Patient
    • 28-y.o. man c/o chronic cough at night (2  /wk); wheezing daily
    • PMHx: Recent onset of mild asthma (1 yr)
    • Current meds: albuterol as needed
    • PE: wheezing
    • Pulmonary function tests
      • FEV 1 : 70% of predicted
      • FEV 1 /FVC = 0.65
      • PEF variability: >30%
    • Diagnosis: moderate, persistent asthma 1
    • Therapy changed: inhaled flunisolide; salmeterol (for nighttime symptoms); inhaled albuterol as needed
    www.RxForSanity.com 1 National Institutes of Health. NAEPP. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. 1997. NIH Publication 97-4051.
  • 33. Asthma Patient: Return Visit
    • 3 months later: PFTs still abnormal, symptoms unchanged
    • High suspicion of nighttime GERD-related asthma 1
      • Adult onset
      • Wheezing worsened by supine position
      • Nighttime cough
      • Heartburn 2 times per week, at night
    • Diagnosis: Nighttime GERD
    www.RxForSanity.com 1 New Considerations in the Education and Management of Gastroesophageal Reflux Disease. [Pamphlet]. Chicago: AMA; 2002.
  • 34. Association of GERD and Asthma www.RxForSanity.com Adapted from Barish CF, et al. Arch Intern Med. 1985;145:1882–1888. Two Basic Mechanisms
  • 35. If you want a guarantee, buy a toaster. The Rookie, 1990 www.RxForSanity.com
  • 36. Some patients with GERD need additional investigations
    • Those with:
    • atypical history
    • reflux symptoms that are frequent and long-standing or do not respond to therapy
    • alarm symptoms:
      • severe dysphagia
      • weight loss
      • bleeding
      • haematemesis
      • mass in the upper abdomen
      • anaemia
    Labenz & Malfertheiner. World J Gastroenterol 2005;11:4291–9
  • 37. Radiology – limited value in the diagnosis of GERD
    • May be helpful for:
    • Detecting subtle strictures and large hiatal hernias in patients with dysphagia.
    • Identifying pathologies unrelated to GERD.
  • 38.
    • Investigate the degree and timing of reflux.
    • Correlate reflux events with symptoms.
    • Limitation: A quarter of patients (6/22) had different reflux patterns (from normal to pathological) when tested 6 weeks apart under identical conditions, due to diurnal variations.
    Investigation of acidic reflux episodes by 24-hour pH-monitoring Franzén & Grahn. Scand J Gastroenterol 2002;37:6–8
  • 39. www.RxForSanity.com
  • 40. The most common findings during endoscopy for GERD 0 10 20 30 40 50 60 Patients (%) Non-erosive reflux disease 57 Reflux esophagitis 31 Barrett's esophagus 12 398 consecutive patients No alarm symptoms Sharma et al. Gastroenterology 2000;122(4 Suppl 1):A-584
  • 41. The GERD symptom pattern is similar in patients with and without reflux esophagitis Belching Bloating Abdominal pain Nausea Regurgitation Heartburn (100%) Epigastric pain Scale=% of patients with symptom Without reflux esophagitis With reflux esophagitis Carlsson et al. Eur J Gastroenterol Hepatol 1998;10:119–24
  • 42. Severity of heartburn is similar in patients with different grades of reflux esophagitis A B C D LA grade of reflux esophagitis Patients with heartburn (%) 0 10 20 30 40 60 50 No heartburn Mild heartburn Moderate heartburn Severe heartburn n=4283 Levine et al. Am J Gastroenterol 1999;94:2591
  • 43. The LA Classification
    • Reflux esophagitis is defined by the presence of definite breaks in the esophageal mucosa, visible by endoscopy:
      • mucosal break – an area of slough or erythema that has discrete demarcation from the mucosa.
    • The extent of reflux esophagitis is described independently of other measures of severity in a clear, simple and highly reproducible way.
    • Complications, such as Barrett’s esophagus or esophageal stricture, are described separately.
    Lundell et al. Gut 1999;45:172–80
  • 44. The Los Angeles Classification system for the endoscopic assessment of reflux esophagitis One (or more) mucosal break, no longer than 5 mm, that does not extend between the tops of two mucosal folds Grade A One (or more) mucosal break, more than 5 mm long, that does not extend between the tops of two mucosal folds Grade B One (or more) mucosal break that is continuous between the tops of two or more mucosal folds, but which involves less than 75% of the circumference Grade C One (or more) mucosal break that involves at least 75% of the esophageal circumference Grade D Lundell et al. Gut 1999;45:172–80
  • 45. LA Grade C www.RxForSanity.com
  • 46. LA Grade B is the most prevalent grade of esophagitis in western countries 34% 39% 20% 7% Grade A Grade B Grade C Grade D El-Serag & Johanson. Scand J Gastroenterol 2002;37:899–904
  • 47. Direct visualisation of the esophageal mucosa by endoscopy
    • Optimal technique for determining the presence and severity of reflux esophagitis.
    • The only reliable technique for detecting endoscopically suspected esophageal metaplasia.
    • Allows biopsy to be performed to confirm histological changes characteristic to Barrett’s esophagus, dysplasia or carcinoma.
    Dent et al. Gut 1999;44(Suppl 2):S1–16
  • 48. Patients with persistent GERD are at risk of esophageal complications GERD Barrett ’s metaplasia Barrett ’s metaplasia with dysplasi a Adenocarcinoma
  • 49. The incidence of esophageal adenocarcinoma is increasing 0 .0 0.6 1. 0 Incidence/100,000 person-years 1950 1960 1980 1970 1990 0 .2 0 .4 0 .8 1.2 1.4 Year Bytzer et al. Am J Gastroenterol 1999;94:86–91
  • 50. Risks of Adenocarcinoma with Nocturnal Reflux
    • The risk of esophageal adenocarcinoma in subjects with weekly nighttime symptoms was
    • ~11x
    • that of controls without weekly nighttime symptoms
    www.RxForSanity.com Lagergren J et al. N Engl J Med . 1999;340:825-831. Freidin N et al. Gut . 1991;32:1275-1279.
  • 51. Esophageal adenocarcinoma risk increases with frequency and severity of GERD symptoms 4 8 1 2 18 Odds ratio for esophageal adenocarcinoma 0 2 6 10 14 20 None 1/week 2–3/week > 3/week 16 None 1–2 2.5–4 4.5–6.5 Frequency of reflux symptoms Symptom severity score Lagergren et al. N Engl J Med 1999;340:825–31
  • 52. Pathophysiology of Barrett’s esophagus
    • Adaptation to the longstanding exposure to excessive amounts of stomach acid and bile.
    • During healing, a metaplastic process occurs in which squamous epithelium is replaced by abnormal columnar epithelium.
    Short segment Barrett’s esophagus
  • 53. Screening for Barrett’s esophagus
    • Alarm symptoms (dysphagia, bleeding, weight loss) and chronic GERD should be referred for endoscopy.
    • A one-time endoscopy to exclude Barrett’s esophagus in 50-year-old patients with GERD has been proposed by some experts as a cost-effective alternative.
  • 54. The prevalence of Barrett’s esophagus increases with the duration of reflux symptoms <1 1–5 5–10 >10 Duration of symptoms (years) Prevalence of endoscopic Barrett's esophagus (%) 0 5 1 0 15 2 0 25 Lieberman et al. Am J Gastroenterol 1997;92:1923–7
  • 55. Barrett’s esophagus is associated with prolonged acid reflux 20 0 5 1 0 15 Number of episodes 0 1 2 3 Time ( minutes) Reflux episodes >5 minutes Mean duration of reflux episode Barrett’s esophagus, n=51 Severe reflux esophagitis, n=30 Moderate reflux esophagitis, n=45 Controls, n=24 Coenraad et al. Am J Gastroenterol 1998;93:1068–72
  • 56. Who is at risk for Barrett’s?
    • 5% to 13% of GERD patients verses <1% unselected patients with EGD
    • More common in white or Hispanic men and less frequent in black and Asian
    • Smoking, obesity are risk factors
  • 57. Different GERD symptoms with Barrett’s?
    • Long history of gastroesophageal reflux disease (GERD)
    • Increased severity of nocturnal reflux symptoms.
    • But... 25 % of patients with Barrett’s esophagus have no reflux symptoms, most probably related to a diminished acid sensitivity.
  • 58. www.RxForSanity.com
  • 59. You improvise. You adapt. You overcome. Heartbreak Ridge 1986 www.RxForSanity.com
  • 60. Premalignant metaplastic process
    • Normal squamous epithelium of the distal esophagus is replaced by columnar epithelium that is more resistant to acid and bile
    Normal squamocolumnar junction between esophagus and stomach Barrett’s esophagus with displaced squamocolumnar junction Squamous epithelium Columnar epithelium
  • 61. Pathology
    • Specialized intestinal metaplasia (SIM).
    • SIM is characterized by the presence of goblet cells.
    Goblet cells Intestinal metaplasia
  • 62.  
  • 63. Short or long?
  • 64. C&M staging for Barrett’s .
  • 65. 90-95% of patients who have Barrett's esophagus will not develop cancer.
  • 66. DR. FOX: Have you been taking your pills every day? McCALEB: Yeah, yeah all 34 of them. Blood Work, 2002 www.RxForSanity.com
  • 67. Goals of Therapy for Nighttime Reflux
    • Prevent, heal esophagitis (or eliminate recurrence)
    • Prevent complications
    • Eliminate symptoms
    • Improve sleep
    www.RxForSanity.com
  • 68. ADLER: Red, they got T-bones in the fridge. And tater tots. I do like tater tots. A Perfect World, 1993 www.RxForSanity.com
  • 69. Therapeutic Modalities Used for GERD and Nighttime Heartburn
    • Lifestyle Modifications
    • OTC Medications
    • Prescription Medications
    www.RxForSanity.com
  • 70. The frequency of reflux symptoms is directly related to the time that the esophageal pH is <4 0 2 3 5 7 8 Intraesophageal acid exposure (% time pH <4) 6 – 9 9 – 12 12 – 15 15 – 18 18 – 21 21 – 24 0 – 3 3 – 6 Time of day (hours) A lmost continuous symptoms Daily symptoms Occasional symptoms H ealthy individuals n=190 1 4 6 Joelsson & Johnsson. Gut 1989;30:1523–5
  • 71. The healing of reflux esophagitis is directly related to the duration of intragastric pH >4 0 20 40 60 80 100 Patients healed after 8 weeks (%) 2 4 6 8 10 12 14 16 18 20 22 Duration intragastric pH >4 ( hours ) Adapted from Bell et al. Digestion 1992;51(Suppl 1):59–67
  • 72. Gastric pepsin activity declines if the pH is raised above 4 0 20 40 60 80 100 Maximum pepsin activity (%) Gastric juice pH 4 3 2 1 . Adapted from Berstad. Scand J Gastroenterol 1970;5:343–8
  • 73. Increased exposure of the esophagus to acidic gastric content is a dominating cause of GERD “ In the majority of people with reflux disease, there is abnormally prolonged exposure of the distal esophagus to acid and pepsin.” “ The dominant mechanism of symptom production in reflux disease is by contact of the esophageal mucosa with acid and pepsin.” Dent et al. Gut 1999;44(Suppl 2):S1–16
  • 74. PPIs and H 2 -receptor antagonists in relieving symptoms in patients with reflux esophagitis 0 20 40 60 Patients free from heartburn (%) 0 1–2 3–4 6–8 Weeks of treatment PPIs H 2 -receptor antagonists n=2198 p<0.0001 8 0 Chiba et al. Gastroenterology 1997;112:1798–810
  • 75. PPIs and H 2 -receptor antagonists in healing of reflux esophagitis p<0.0005 0 20 40 60 80 Reflux esophagitis cases healed (%) 0 2 4 6 8 10 12 Time (weeks) PPIs H 2 -receptor antagonists Placebo 100 Chiba et al. Gastroenterology 1997;112:1798–810
  • 76. H 2 -receptor antagonists inhibit signal transduction to the proton pump Proton pump Signal transduction to activate proton pump H + Acid secretion Parietal cell Histamine receptor Histamine (H 2 )-receptor antagonist Histamine Inhibition of histamine receptor Gastric gland Blood
  • 77. PPIs control acid secretion by directly inhibiting the proton pump Inhibition of acid secretion Parietal cell Canalicular space Proton pump Inhibition of proton pump Activation Concentration PPI (inactive) H + Blood Gastric gland
  • 78. Symptom response may be a useful indicator of healing of reflux esophagitis “ In more than 75% of patients with esophagitis who present with frequent episodes of symptoms, control of heartburn to less than two episodes per week with therapy is associated with healing of esophagitis.” Genval statement 62, accepted with some reservation Dent et al. Gut 1999;44(Suppl 2):S1–16
  • 79. Progression and regression of GERD
    • Relapse or regression of endoscopic findings under routine care, without relation to symptoms, over 2 years.
    * No erosions Labenz et al. Am J Gastroenterol 2006;101:2457 – 62 NERD n=1717 74.5% *50.4% *61.3% 24.9% 0.6% 1.6% Los Angeles A/B n=1512 Los Angeles C/D n=278 7.8% 37.1% 41.8%
  • 80. Clyde, sometimes I think you're not too tightly wrapped. Any Which Way You Can, 1980 www.RxForSanity.com
  • 81. Areas to Explore to Uncover Nighttime Reflux
    • Assessment of nighttime-associated symptoms: heartburn, regurgitation, chronic cough/hoarseness, difficulty breathing, wheezing, or frequent throat clearing
    • Effect of position on symptom(s) (i.e., recumbent vs. upright)
    • Effect of symptom(s) on sleep (i.e., falling asleep, staying asleep, waking refreshed)
    • History and efficacy of patient ’ s symptom management
    www.RxForSanity.com
  • 82. The GERD, the Bed, and the Ugly
    • Why is nighttime a period of risk for reflux complications?
      • Protective mechanisms reduced/absent = prolonged esophageal exposure to refluxate
    • What symptoms are linked to nighttime reflux?
      • Nighttime asthma/cough, sleep disturbance, etc.
    • What areas should be explored to effectively diagnose nighttime reflux?
      • Effect on sleep, positional dependency
    • How should nighttime reflux be managed?
      • Acid suppression, possibly lifestyle modification
    www.RxForSanity.com
  • 83. Go ahead, make my day. Sudden Impact, 1983 www.RxForSanity.com
  • 84. RxForSanity.com Visit today for a FREE subscription to our eZine, with monthly medical humor and new educational presentations! www.RxForSanity.com