Nighttime GERD: Clinical implications and therapeutic challenges

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<ul><li><p>It is estimated that 7% of the individuals in the general population in United Statesexperience heartburn the cardinal symptoms of this disease daily, whereas 14% have</p><p>1,2</p><p>Best Practice &amp; Research Clinical GastroenterologyVol. 18, No. S, pp. 3138, 2004</p><p>doi:10.1016/j.bpg.2004.06.010available online at</p><p>* Tel.: C1-414-456-6840; Fax: C1-414-456-6215.E-mail address: rshaker@mcw.eduGERD symptoms at least once a week.A considerable amount of information exist about the prevalence of GERD in</p><p>general, however, data specifically addressing nocturnal reflux is limited.36</p><p>For example, it was only recently reported3 that prevalence of nocturnal heartburn,Nighttime GERD: Clinical implications</p><p>and therapeutic challenges</p><p>Reza Shaker*Professor</p><p>Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave.,</p><p>Milwaukee, WI 53226, USA</p><p>Limited available data specifically addressing nocturnal gastroesophageal reflux indicate itsassociation with more severe injuries such as esophagitis and stricture, adenocarcinoma of theesophagus, respiratory and ENT disorders as well as sleep disturbances, diminished quality of lifeand undesired changes in activities of daily living.In a recent survey, altogether 79% of respondents reported experiencing heartburn at night.Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburnnegatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impairedtheir ability to function the following day. Of the 791 respondents with nighttime heartburn, 71%reported taking over-the-counter medicine for it, only 29% of these rated this approachextremely effective. Forty-one percent reported trying prescription medicines and 49% of theserated this approach extremely satisfactory.This recent understanding of the prevalence and impact of nighttime heartburn is an indicator ofnocturnal acid reflux events and suggests that nighttime heartburn occurs in a large majority ofadults with gastroesophageal reflux disease. The fact that expected result from implementedtherapy for heartburn is not achieved by a sizable percentage of patients can have significantmanagement implications.</p><p>Key words: gastroesophageal reflux disease; adenocarcinoma; nighttime heartburn.</p><p>Gastroesophageal reflux disease (GERD) is the most common malady of the esophagus.1521-6918/$ - see front matter Q 2004 Published by Elsevier Ltd.</p></li><li><p>the cardinal symptom of reflux disease among individuals suffering from chronicheartburn, is at an unexpected level of 74%. In addition, this study3 demonstrated a</p><p>32 R. Shakersignificantly more negative impact on quality of life in nocturnal heartburn suffererscompared to those with diurnal symptoms. Nocturnal acid reflux is reported to beassociated with more severe reflux induced injuries such as esophagitis and stricture46,as well as adenocarcinoma of the esophagus7, respiratory and ENT disorders as well assleep disturbances, diminished quality of life and undesired changes in activities of dailyliving. Furthermore, considering the reports indicating reasonable specificity ofheartburn for diagnosis of GERD8, a better understanding of the prevalence andimpact of nocturnal heartburn can have significant potential diagnostic and managementimplications. A national population-based telephone interview survey of 1000 adults, 18years of age or older, who reported experiencing heartburn at least once a weekconducted by The Gallup Organization on behalf of The American GastroenterologicalAssociation, evaluated (a) the prevalence of nighttime heartburn and reflux attributedsupraesophageal symptoms among patients with GERD and (b) the impact of nighttimeheartburn on sleep and some of the activities of daily living that could impact the qualityof life. The survey also allowed for collection of additional information aboutconcomitant respiratory symptoms, use of medication and seeking medical help.</p><p>Of the 1000 respondents, irrespective of time, about one-quarter reportedexperiencing heartburn once or more each day, 43% reported experiencing heartburn12 times per week, and 20% 36 times per week. Thirteen percent of the respondentscould not quantify the frequency of their heartburn episodes.</p><p>Chronicity of heartburn varied widely, with heartburn experienced at least once aweek. While nearly one-third of the respondents reported experiencing heartburn for10 years or longer, a total of 15% of respondents reported that their heartburn hadbeen present for only a year or less. Over 50% reported experiencing heartburnbetween 2 and 10 years.</p><p>Frequency of the reported nighttime and daytime heartburn is summarized inFigure 1. As seen, 13% of the respondents reported experiencing heartburn only duringnighttime, whereas 20% reported heartburn only during daytime. Sixty-five percent ofrespondents experienced heartburn both day and night. Altogether, 79% of theheartburn sufferers reported experiencing heartburn at night.</p><p>A large percentage of the respondents reported concomitant symptoms, potentiallyattributable to gastroesophageal reflux. Throat clearing was reported by 39% of the1000 respondents, while chronic cough, hoarse voice and asthma were reported by 16,18 and 13%, respectively. In addition, a burning sensation in the throat was reported by50%.</p><p>When inquired about the effect of heartburn on sleep, among respondents withnighttime heartburn, 75% reported that the symptom affected their sleep, and 63%believed that heartburn negatively affected their ability to sleep well. Forty percent ofrespondents with nocturnal heartburn believed that the sleep difficulties due to thenighttime heartburn impaired their ability to function the following day. Prevalence ofsleep disturbances among respondents increased with the increase in frequency of thenighttime heartburn episodes during the week (Figure 2).</p><p>Forty-two percent of the respondents stated that they have accepted the fact thatthey cannot sleep through the night, 39% reported that they take naps wheneverpossible, and 34% reported sleeping in a chair or in a seated position. Surprisingly, 27%reported that their heartburn-induced sleep disturbances kept their spouses fromhaving a good nights sleep. In general, heartburn resulted in some degree of limitationor change in lifestyle of the respondents. Over half reported that heartburn caused</p></li><li><p>Daytime &amp;Nighttime</p><p>Nighttimeonly</p><p>Daytimeonly</p><p>Do notknow</p><p>13%20%</p><p>2%</p><p>65%</p><p>(n=1000)</p><p>100</p><p>90</p><p>80</p><p>70</p><p>60</p><p>50</p><p>40</p><p>30</p><p>20</p><p>10</p><p>0</p><p>% W</p><p>ith H</p><p>eartb</p><p>urn</p><p>Figure 1. Prevalence of nighttime and daytime heartburn. As seen, the majority of respondents experienced</p><p>both nighttime and daytime heartburn. However, a minority reported either nighttime or daytime heartburn.</p><p>In total, 79% of respondents reported experiencing nocturnal heartburn.</p><p>Gastroesophageal reflux disease 33changes in the time, nature and quantity of their food intake. Tables 1 and 2 representsome of the effects of heartburn on the lifestyle of respondents.</p><p>A variety of medical and non-medical approaches to heartburn were reported by therespondents. Surprisingly, of the 791 respondents with nighttime heartburn about30% of respondents did not report taking any kind of medication, 71% reported takingover-the-counter medication for their heartburn, while 41% reported tryingprescription medicines. Altogether, the efficiency of remedies for heartburn was80</p><p>70</p><p>60</p><p>50</p><p>40</p><p>30</p><p>20</p><p>10</p><p>0</p><p>% W</p><p>ith H</p><p>eartb</p><p>urn</p><p>&lt; Once 1 2x 3x</p><p>Kept awake (n=453)</p><p>Woke up duringnight (n=454)</p><p>Heartburn Episodes/Week</p><p>44%41%</p><p>53% 54%</p><p>67% 70%</p><p>Figure 2. The frequency of sleep difficulties increased with an increase in the frequency of heartburn</p><p>experienced each week by respondents. Over two-thirds of those who experienced heartburn three times or</p><p>more per week reported being kept awake or being wakened during the night because of heartburn.</p></li><li><p>Table 1. Daily life affected by heartburn.</p><p>34 R. ShakerGreatly</p><p>(%)</p><p>Quite a</p><p>bit (%)</p><p>Moder-</p><p>ately (%)</p><p>Mildly</p><p>(%)</p><p>Not at</p><p>all (%)</p><p>DK/RF</p><p>(%)</p><p>Total</p><p>(%)</p><p>Ability to eat or</p><p>drink what you want</p><p>15 10 21 20 33 1 100</p><p>Ability to get a good</p><p>nights sleep</p><p>11 8 21 23 36 1 100</p><p>Ability to eat or</p><p>drink when you want</p><p>11 7 19 23 39 1 100</p><p>Ability to sleep when</p><p>you want</p><p>9 7 19 21 43 1 100</p><p>Your mood or</p><p>general well-being</p><p>8 8 19 22 42 1 100</p><p>Social activities 7 4 12 16 59 2 100</p><p>Spouses ability to</p><p>get a good nights</p><p>sleep</p><p>5 2 10 10 55 18 100</p><p>Ability to function</p><p>day-to-day</p><p>4 4 17 23 51 1 100</p><p>Ability to function</p><p>well at work the</p><p>next day</p><p>4 4 15 17 48 12 100variable. Only 29% of those taking over-the-counter, and 42% of those takingprescription medicine rated these approaches completely satisfactory. Other measurestaken by respondents and their effectiveness are summarized in Figure 3.</p><p>The findings of this survey taken together with that of a previous report by Farupet al3 suggest that both the prevalence and the impact of nighttime heartburn have beenunderestimated, and that the symptom often is not treated adequately. These issueshave practical implications for the management of GERD in that they highlight severalimportant features of the disease: (1) only a minority of heartburn sufferers seekmedical help and are on adequate treatment, (2) although only a minority experiencenighttime heartburn exclusively almost 8 of 10 of those who report frequent heartburnexperience nighttime heartburn, and most patients have the symptom both during theday and at night, (3) it seems that the condition impairs sleep, and consequently has asubstantial negative impact on daily function and lifestyle. These findings suggest a needfor more specific inquiry about nocturnal reflux form patients and more effort inrecognising and treating the nocturnal manifestations of GERD.</p><p>Esophageal acid clearance is a two-step process and involves (a) volume clearanceand (b) acid neutralization.9,10 In this process, the majority of the refluxed gastric acid iscleared from the esophagus by either primary or secondary peristalsis, while theresidual hydrogen ion that remains behind is neutralized by salivary bicarbonate and, toa lesser extent, by bicarbonate secreted from the esophageal submucosal glands.11</p><p>During sleep acid clearance is curtailed. Swallowing virtually ceases during sleep and,consequently, primary peristalsis (that is induced by swallowing) is not stimulated.</p><p>DK, do not know; RF, refused to answer. Experiencing heartburn affected a number of activities of daily</p><p>living and social functions of the responders. These included their eating, sleeping, social life and work.</p></li><li><p>Table 2. How respondents treated their heartburn.</p><p>Gastroesophageal reflux disease 35All with heart-</p><p>burn (%)</p><p>Prescription</p><p>medication (%)</p><p>Over-the-counter</p><p>medication (%)</p><p>No medi-</p><p>cation (%)</p><p>Changed foods eaten 56 63 56 45</p><p>Eating smaller meals and</p><p>more often</p><p>50 56 50 44</p><p>Propped up head for</p><p>sleeping</p><p>48 58 43 41</p><p>Reduced stress 43 47 40 42</p><p>Accepted that cannot</p><p>sleep through the night</p><p>42 43 43 39</p><p>Take naps when possible 39 39 37 41</p><p>Sleep in chair or sitting</p><p>position</p><p>34 41 28 31</p><p>Reduced or quit drinking</p><p>alcohol</p><p>29 29 29 27</p><p>Changed frequency of</p><p>exercise</p><p>25 29 22 22</p><p>Quit smoking 14 14 15 14</p><p>Number of interviews 1000 386 340 274Therefore, esophageal volume clearance during sleep is almost totally a function ofsecondary peristalsis that may not be stimulated by the reflux of small amounts ofgastric content. Experimental data suggest that a threshold volume ranging between 5and 30 ml is required to stimulate secondary peristalsis in healthy individuals.12</p><p>Furthermore, the triggering mechanism of secondary peristalsis among healthy elderlyindividuals13 and among patients with reflux esophagitis is deteriorated.14,15 Therefore,volume clearance of refluxed gastric acid during sleep may not be as reliable as in awakestate. In addition, not only recumbent position during sleep facilitates reflux, the effectof gravity after the reflux event retards esophageal clearance for individuals in therecumbent position. The cessation of swallowing during sleep also impairs acidclearance because there is no salivary bicarbonate available to neutralize hydrochloricacid dissolved in the esophageal unstirred water layer. Consequently as a result of thereduction in esophageal volume clearance and acid neutralization during sleep,nocturnal acid reflux might be especially damaging to the esophagus because theacid will have prolonged contact with the mucosa. Indeed, several studies havedocumented recumbent nocturnal acid exposure among the majority of patients withsevere consequences of reflux disease such as Barretts esophagus and erosiveesophagitis.1619 In addition, the reduced esophageal peristaltic activity may predisposeto proximal migration of the acid refluxate23, thereby increasing the likelihood ofdamage to the oropharynx and airway.</p><p>Lifestyle changes made due to heartburn symptoms among all respondents, those taking prescription</p><p>medicine, those taking over-the-counter medicine and those who did not report taking any medicine. As</p><p>seen across the board, except for changes in frequency of exercise and smoking, one-third to one-half of</p><p>respondents from all groups reported that they have made various changes in their activities of daily living</p><p>and lifestyle due to heartburn.</p></li><li><p>70</p><p>60</p><p>50</p><p>40</p><p>30</p><p>20</p><p>10</p><p>0</p><p>%</p><p>W</p><p>i</p><p>t</p><p>h</p><p>H</p><p>e</p><p>a</p><p>r</p><p>t</p><p>b</p><p>u</p><p>r</p><p>n</p><p>OTCMedication</p><p>AvoidingFood Before</p><p>Bed</p><p>Eating orDrinking</p><p>Something</p><p>ElevatingHead of</p><p>Bed</p><p>PrescriptionMedications</p><p>SleepingSitting up</p><p>Taking Pills</p><p>Sleeping</p><p>Tried this method</p><p>Completely satisfied withthis method</p><p>(n = 791)</p><p>71%</p><p>29%</p><p>61%</p><p>33%</p><p>52%</p><p>15%</p><p>44%</p><p>23%</p><p>41%49%</p><p>27% 27%</p><p>16%</p><p>29%</p><p>Figure 3. Action taken by those experiencing nighttime heartburn. As seen, only half of those who took prescription medication and one-third of those who used over-the-</p><p>counter medications reported the results to be completely satisfied. Across the board, for other actions the results were less satisfactory.</p><p>36</p><p>R.Sh</p><p>aker</p></li><li><p>Information about the prevalence of nocturnal heartburn is scarce. Availablestudies3 have reported a 10% overall prevalence for nocturnal GERD symptoms in</p><p>serious conditions such as malignancy inducing the respiratory symptoms need to beruled out before these symptoms are attributed to reflux disease.</p><p>One of the unexpected findings of the available studies is the percentage of</p><p>Gastroesophageal reflux disease 37respondents who are dissatisfied with their GERD therapy, including both prescriptionand over-the-counter medications. In one survey20, among 70% of respondents whoreported taking any medication, less than half expressed satisfaction. More surprisingwas the percentage (15%) of those who used over-the-counter medication in additionto prescription drugs, suggesting either inadequate dosage or inappropriate usage ortiming of the latter.</p><p>A troublesome consequence of nighttime heartburn is sleep disturbances and itsnegative impact on the next day function.20 Especially disturbing is the limiting effect thatnighttime heartburn is reported to have on personal and social activities of the studiedpopulation.20 The socioeconomi...</p></li></ul>