Introduction

Recently, there has been an increase in the number of patients with gastroesophageal reflux disease (GERD) in Japan [1–4]. Patients with GERD symptoms can be divided into 2 groups; those with and without endoscopically proven mucosal breaks. Patients with mucosal breaks have been classified as showing reflux esophagitis (RE), and RE can be divided into 2 grades; low-grade RE (grades A and B in the Los Angeles classification) and high-grade RE (grades C and D) based on the form of the mucosal breaks [5]. On the other hand, patients with reflux symptoms but without mucosal breaks have been classified as showing non-erosive reflux disease (NERD) and functional heartburn [6, 7].

GERD-related symptoms have a major impact on quality of life [8, 9]. Heartburn and acid regurgitation are referred to as typical GERD symptoms, while other symptoms reported by GERD patients, such as epigastralgia, an epigastric burning sensation, abdominal fullness, cough, hoarseness, and chest pain, are considered to be atypical symptoms [10–12]. Several studies have suggested that the typical symptoms are less common and the atypical symptoms more common in elderly patients with GERD [13–19]. Although previous studies have investigated elderly patients with GERD, few have compared the symptoms reported by elderly patients with and without esophageal mucosal breaks [17, 19]. In addition, the characteristics of symptoms in elderly Asian GERD patients have not been fully determined. Therefore, we performed this study to clarify the prevalence of typical and atypical symptoms in elderly and non-elderly patients with different types of GERD.

Subjects and methods

This study was approved by the ethics committee of Shimane University Faculty of Medicine and was carried out in accordance with the Declaration of Helsinki. We prospectively enrolled in the study outpatients who visited 13 medical centers and clinics in western Japan, because of the presence of several upper gastrointestinal symptoms, consecutively from April 2009 to September 2009. Individuals with a history of gastric surgery were not included in this study, and patients who had taken proton pump inhibitors, H2 receptor antagonists, or prokinetic agents in the preceding 2 months were also excluded. However, patients who took other medications for the treatment of complicated diseases were included in this study. Four hundred and thirty-eight patients were enrolled in this study during the study period. All 438 patients were asked: “Which symptoms do you have of the symptoms of heartburn, regurgitation, an epigastric burning sensation, epigastralgia, epigastric discomfort, abdominal fullness, and others?” to which they responded “yes” or “no” to each question. In addition, the patients were asked to report all of their symptoms in order from the most to least bothersome. Next, they were asked: “When do you most frequently experience bothersome symptoms?” For this study, the symptoms of heartburn and acid regurgitation were defined as typical symptoms of GERD, and the symptoms of an epigastric burning sensation, epigastralgia, epigastric discomfort, abdominal fullness, nausea, vomiting, belching, dysphagia, and ‘others’ were defined as atypical symptoms. Three hundred and forty of the 438 patients had heartburn and/or acid regurgitation. Therefore, in this study, we regarded these 340 patients as having GERD (185 men, 155 women; mean age 62.2 ± 14.5 years) and we analyzed findings in these patients after dividing them into elderly (≥65 years) and non-elderly (<65 years) groups.

All patients were examined by upper gastrointestinal endoscopy, and the condition was classified as RE or non-RE based on the presence or absence of esophageal mucosal breaks. The RE was further classified as grade A, B, C, or D according to the Los Angeles classification [5], with grades A and B classified as low-grade RE, and grades C and D as high-grade RE.

Statistical analysis was performed using the χ2 test for comparisons between the groups. The Mann–Whitney U-test was also applied when a significant difference was observed using the Kruskal–Wallis test. Multiple logistic regression analysis was also used to calculate the odds ratios. All calculations were done with the Stat View 5.0 software package for Macintosh (Abacus Concepts, Berkeley, CA, USA). Differences at P < 0.05 were considered to be statistically significant.

Results

In the 340 patients with GERD enrolled in this study, the numbers of patients without mucosal breaks, with low-grade RE, and with high-grade RE were 158, 147, and 35, respectively. No significant difference in the proportion of males and females was found in regard to these classifications. The numbers of elderly (≥65 years old) and non-elderly (<65 years), a patients were 161 and 179, respectively. Fifty-eight percent of the elderly patients and 35% of the non-elderly patients were female, and this difference was significant. In the elderly group, 12.4% had high-grade RE as compared to 8.4% in the non-elderly group (Table 1).

Table 1 Clinical characteristics of enrolled patients
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Typical GERD symptoms (heartburn and acid regurgitation) were mainly noted as the most bothersome symptoms by our study subjects. However, many patients also had atypical GERD symptoms, such as an epigastric burning sensation, epigastralgia, epigastric discomfort, and abdominal fullness (Table 2). When the symptoms were considered according to the presence of mucosal breaks, elderly patients without mucosal breaks more frequently reported typical GERD symptoms as bothersome, and less frequently complained of atypical GERD symptoms, as compared with the non-elderly patients without mucosal breaks. There was no significant difference in the prevalence of typical and atypical GERD-related symptoms between the elderly and non-elderly patients with mucosal breaks (Table 3). Multiple logistic regression analysis revealed that younger age and absence of esophageal mucosal breaks were significant risk factors for the presence of atypical GERD symptoms in patients with GERD (Table 4).

Table 2 Upper GI symptoms in GERD patients
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Table 3 Symptoms reported by elderly and non-elderly GERD patients
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Table 4 Multiple logistic analysis for the presence of atypical GERD symptoms
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The times of day when the symptoms occurred are summarized in Table 5. Bothersome symptoms in the elderly patients with low-grade RE occurred more frequently after meals and less frequently at night. There was no significant difference in regard to the time of day when the bothersome symptoms occurred between the elderly and non-elderly patients without mucosal breaks, or between the elderly and non-elderly patients with high-grade RE.

Table 5 Time of day when bothersome symptoms frequently occurred in elderly and non-elderly GERD patients
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Discussion

Several groups have previously investigated the characteristics of symptoms in elderly patients with GERD [13–19]. Those previous studies, performed mainly in western countries, demonstrated that the esophageal lesions and symptoms in elderly patients with GERD were somewhat different from those in non-elderly patients; thus, there is a possibility of different results in elderly and non-elderly Asian individuals also. In the present study, we investigated the symptoms of elderly and non-elderly patients with different types of GERD, and we found that atypical GERD symptoms, such as an epigastric burning sensation, epigastralgia, epigastric discomfort, and abdominal fullness, were frequently reported by non-elderly patients without mucosal breaks. In contrast, elderly patients with GERD less frequently had atypical GERD symptoms, even if they did not have esophageal mucosal breaks. Räihä et al. [14] speculated that elderly patients do not frequently report typical symptoms such as heartburn and acid regurgitation. In addition, Mold et al. [15] noted that atypical symptoms, such as vomiting, anorexia, dysphagia, respiratory symptoms, belching, dyspepsia, hoarseness, and postprandial fullness, were commonly reported by elderly patients with GERD. Decreased esophageal sensitivity to esophageal dilatation and intra-esophageal acid has been demonstrated to reduce GERD symptoms in elderly patients [20, 21]. Indeed, elderly Japanese patients with RE were also reported to have typical GERD symptoms less frequently and less severely than non-elderly patients [18]. In addition, increased disability or frailty associated with aging was suggested to influence symptomatic expression in elderly GERD patients [13, 15]. The results of the present study did not fit well with the results of these previous studies, because our elderly patients with GERD had atypical GERD symptoms less frequently than the non-elderly patients. This difference may reflect differences in the characteristics of the patients enrolled in the previous studies and those enrolled in our study, as the study subjects in almost all the previous studies were patients who had endoscopically proven RE [13–19]. In contrast, our study subjects were all symptomatic patients, whereas non-symptomatic elderly patients with RE were not included in our study.

In the present study, the percentage of patients who complained of typical GERD symptoms as their most troublesome ones was low and it was less than 70% only in the non-elderly GERD patients without mucosal breaks (Table 3). The prevalence of functional dyspepsia is known to be higher in the non-elderly population [22], and the number of patients with non-erosive GERD associated with functional dyspepsia is expected to be particularly high in the non-elderly population. Therefore, these non-elderly patients may complain of dyspepsia symptoms but not typical GERD symptoms as their most troublesome symptoms.

Elderly patients have been shown to have a higher grade of GERD, as manifested by larger mucosal injuries, as compared to non-elderly patients [1, 16, 19, 23]. Zhu et al. [16] reported that 21% of elderly patients with GERD had grade III–IV erosive lesions, based on the Savary-Miller criteria, as compared with only 3.4% of non-elderly patients (P < 0.002). In the present study, the proportion of patients with high-grade RE in the elderly group (12.4%) was higher than that in the non-elderly group (8.4%); this finding confirmed the observations of Zhu et al. [16], as well as confirming findings reported in Japan [1, 2, 18, 23, 24].

Transient lower esophageal sphincter (LES) relaxations that occur mainly in the postprandial period constitute the major mechanism of symptomatic acid reflux in both healthy individuals and patients with GERD [25–28]. However, in a small but significant minority of patients, predominantly those with high-grade esophagitis, acid reflux is associated with straining, or it occurs during periods when basal LES pressure is absent [29–31]. Patients with low-grade RE predominantly have daytime reflux, whereas those with high-grade RE predominantly experience nocturnal reflux, as we have reported previously [5, 24]. Therefore, it is speculated that GERD symptoms reported by patients with low-grade RE mainly occur in the daytime and patients with high-grade RE mainly experience these symptoms in the nocturnal period. The present results, however, did not reveal a significant difference in the percentage of patients who reported postprandial bothersome symptoms when patients were stratified by different endoscopic findings. In addition, there was no significant difference in the percentage of patients who reported bothersome symptoms at night between the groups with different grades of RE. Therefore, different from our expectation, patients with high-grade RE complained about reflux symptoms that mainly occurred in the postprandial period, similar to patients with low-grade RE. When we compared the times of day when elderly and non-elderly patients reported reflux symptoms, there was no significant difference between them, except for a small difference in patients with low-grade RE. Elderly patients with low-grade RE had postprandial symptoms more frequently and nocturnal symptoms less frequently. The clinical implication of this observation is that elderly patients with GERD frequently experience typical reflux symptoms in the postprandial period, as do the non-elderly patients with GERD.

There are some limitations of this study. Firstly, we did not exclude all the patients who were on any kinds of drugs. Therefore, the symptoms complained of by the enrolled patients may have been influenced by the concomitantly administered drugs. Although it is difficult to find elderly patients who are not taking any drugs, a future study focusing only on such drug-free patients will be necessary. Secondly, we did not investigate for the presence of hiatal hernia or the timing of meals in individual patients in this study. The presence of a hiatal hernia has repeatedly been demonstrated to affect LES function, which could be related to symptomatic gastro-esophageal reflux. The relationship between the time of eating a meal and the occurrence of GERD symptoms seems to be very important, as eating a meal prior to sleeping is reported to increase the GERD symptoms caused by acid reflux [32]. Therefore, further study is recommended to clarify the influence of hiatal hernia, eating habits, and the timing of occurrence of GERD symptoms.

In conclusion, atypical GERD symptoms were frequently observed in non-elderly patients with non-erosive GERD. GERD symptoms in the elderly patients occurred mainly in the postprandial period, as did those in the non-elderly patients.