Heartburn
2005; Elsevier BV; Volume: 127; Issue: 5 Linguagem: Inglês
10.1378/chest.127.5.1486
ISSN1931-3543
Autores Tópico(s)Neuroscience of respiration and sleep
ResumoHeartburn has long been largely trivialized in the medical community. It has had a bit of a Rodney Dangerfield reputation in that it “gets no respect!” Primary care physicians treat symptoms of heartburn quite readily with antacids and varying degrees of acid-suppressing drugs ranging from H2 blockers to proton-pump inhibitors, depending on the severity and refractoriness of the symptom. The generally excellent clinical response to symptoms of daytime heartburn has contributed to a notable lack of interest in nighttime gastroesophageal reflux (GER). It is a common clinical observation that patients who have been successfully treated for heartburn complaints will spontaneously report that they are sleeping better. This observation has focused the attention of both researchers and clinicians on the relationship between GER and sleep, as well as on the importance of sleep in the patient's quality of life. Despite this, and the burgeoning body of evidence suggesting that sleep-related GER is an important factor in both the esophageal and respiratory complications of GER, the role of sleep in the clinical presentation of GER has been largely ignored. Considerable clinical attention has more recently been focused on the importance of the symptom of nighttime heartburn, and the concomitant occurrence of nighttime GER. For example, two epidemiologic studies1Shaker R Castell DO Schoenfeld PS et al.Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association.Am J Gastroenterol. 2003; 98: 1487-1493Crossref PubMed Scopus (375) Google Scholar, 2Farup C Leinman 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: 45-52Crossref PubMed Scopus (310) Google Scholar have focused more attention on the occurrence of the symptom of nighttime heartburn. These studies showed remarkable similarity in that they both noted that symptoms of nighttime heartburn are common (about 75% of patients) and that nighttime heartburn was a more bothersome symptom. Furthermore, a portion of these patients reported that nighttime heartburn interfered with their sleep and daytime performance. Other epidemiologic data have shown a strong link between the occurrence of nighttime heartburn (ie, two times a week or more) and respiratory symptoms and sleep disturbance.3Gislason 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: 158-163Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar, 4Jason C Gislason T De Becker W et al.Prevalence of sleep disturbance among young adults in three European countries.Sleep. 1995; : 589-597PubMed Google Scholar The excellent study by Fass and colleagues in the current issue of CHEST (1658) adds considerable support and credibility to the above-noted previous studies. The study included > 15,000 subjects who were participants in other large ongoing clinical trials. The subject pool in this study was several times larger than that of any of the previously cited studies. This alone adds considerable credence to their findings. To their credit, they framed questions concerning nighttime heartburn in a way that would create face validity for the occurrence of this phenomenon during sleep. That is, their question was phrased, “in the past year, how often, on average, have you been awakened during the night with heartburn or indigestion?” An affirmative response to this question would be more likely to reflect an episode of GER that did occur during sleep. In some studies, nighttime heartburn could include an interval of time when an individual may be lying in bed prior to sleep. This study clearly documented a strong relationship between nighttime heartburn and all variables associated with disturbed sleep. Specifically, complaints related to daytime sleepiness appeared to be significantly associated with nighttime heartburn. Also a strong relationship was noted between the symptoms of sleep apnea, such as snoring and daytime sleepiness, and nighttime heartburn. Not surprisingly, body mass index was also a significant predictor of nighttime heartburn. Other variables that have been reported to have a significant association with nighttime heartburn were both self-reported hypertension and asthma as well as the use of benzodiazepines. This is not particularly surprising in view of the now well-established relationship between asthma and GER, as well as among obstructive sleep apnea, GER, and hypertension.5Harding SM Guzzo MR Richter JE The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms.Am J Respir Crit Care Med. 2002; 162: 34-39Crossref Scopus (216) Google Scholar, 6Ing AJ Ngu MC Breslin AB Obstructive sleep apnea and gastroesophageal reflux.Am J Med. 2000; 108(suppl): 120S-125SAbstract Full Text Full Text PDF Scopus (213) Google Scholar, 7Peppard PE Young T Plata M et al.Prospective study of the association between sleep-disordered breathing and hypertension.N Engl J Med. 2000; 342: 1378-1384Crossref PubMed Scopus (4000) Google Scholar Certainly, the logical conclusion that would be drawn from the increased use of benzodiazepines would be an effort to treat sleep disturbances, particularly insomnia. These data, as well as the provocative and interesting study presented by Fass and colleagues, raise the question as to the clinical significance and importance of nighttime heartburn. The first, and perhaps most obvious, question pertains to whether heartburn is really different in the daytime vs the nighttime, or whether it is only a matter of timing. Data by Fass et al did not directly address the issue of whether the variables noted might also predict daytime heartburn. Thus, we are left with the question as to whether any of these variables uniquely predict nighttime heartburn. If indeed this were the case, a very strong argument would be made for the fact that nighttime heartburn is indeed a different entity. Certainly, there are abundant physiologic data to demonstrate that sleep-related GER is responded to physiologically quite differently than daytime GER, although the sensation and experience of heartburn is not notably different. For example, the pattern of daytime GER is quite different from that occurring during sleep.8De Meester TR Johnson LF Joseph GJ et al.Patterns of gastroesophageal reflux in health and disease.Ann Surg. 1976; 184: 459-470Crossref PubMed Scopus (655) Google Scholar The pattern of GER in the daytime is noted to be primarily postprandial and associated with episodes of short duration, while the pattern associated with sleep-related GER is one of fewer episodes with a marked prolongation in the acid clearance time. This pattern of reflux, most notably the supine or nighttime GER events, has been shown to be associated with more severe forms of esophagitis and the complications of GER.9Orr 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: 509-512PubMed Google Scholar, 10Dhiman RK Saraswat VA Mishra A et al.Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease.Dig Dis Sci. 1996; 41: 764-772Crossref PubMed Scopus (23) Google Scholar These associated complications appear to be the result of several features of the esophageal acid mucosal response that are associated with sleep. Three key elements of the waking response to acid mucosal contact are quite clearly altered during sleep.11Orr WC Sleep and gastroesophageal reflux disease: a wake-up call.Rev Gastroenterol Disord. 2004; 1: S25-S32Google Scholar First, there is no “warning signal” since heartburn is a waking conscious phenomenon. The swallowing rate is quite markedly diminished during sleep, and the production of saliva, which is essential for acid neutralization, is also markedly suppressed during sleep. Also, the prolongation of acid mucosal contact associated with sleep-related GER is associated with greater a back-diffusion of hydrogen ions into the esophageal mucosa.12Johnson LF Harmon JW Experiment esophagitis in a rabbit model: clinical relevance.J Clin Gastroenterol. 1986; 8(suppl): 26-44Crossref Scopus (79) Google Scholar It would seem clear from the available data that sleep-related GER is a much more “malignant” form of reflux. Unfortunately, the occurrence of sleep-related GER is not always associated with the symptom of nighttime heartburn. Thus, the occurrence of nighttime heartburn would appear to be a fairly sensitive, but not a very specific, symptom. The reason for this has to do with the phenomenology of sleep itself. Events that occur in and around brief arousals from sleep are poorly recalled. Thus, an individual patient who reports nighttime heartburn perhaps once a week may indeed be experiencing sleep-related GER and its attendant complications much more frequently. Given the fact that relying on the symptom and frequency of nighttime heartburn may not provide a totally accurate reflection of the occurrence of sleep-related GER, what other symptoms or clinical clues may be present to more accurately predict the frequency and clinical significance of nighttime heartburn? As has been noted above, nighttime heartburn has significant associations with other symptoms such as wheezing or coughing, and sleep disturbances. Patients who complain of bothersome daytime heartburn who deny nighttime heartburn should be further queried as to the presence of other possibly sleep-related symptoms. These would include awakening from sleep with coughing or an acidic taste in the mouth, as well as frequent arousals from sleep and unrefreshed sleep. In fact, it is not unreasonable to postulate that GER could be a cause of sleep disturbance in individuals with sleep complaints without other obvious causes such as obstructive sleep apnea. The study by Fass and colleagues has given further credence to the notion that the occurrence of nighttime heartburn is a particularly important clinical manifestation of GER. The perspicacious clinician should be aware that nighttime heartburn, when occurring with a frequency of once a week or more, is an important clue to the existence of a malignant form of GER, as well as of the possibility that GER may be causing other symptoms such as cough, sleep disturbance, and the exacerbation of asthmatic symptoms.
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