Correlation between symptomatic improvement and quality of life in patients with reflux and dyspeptic symptoms.

We investigated the correlation between symptomatic improvement and quality of life in Japanese gastroesophageal reflux disease patients with PPI. Eighty one patients with reflux and dyspeptic symptom were enrolled. The evaluation of the symptom was used he Frequency Scale for the Symptom of GERD in 3 categories: total score of 12 questions, score related to reflux symptoms, and score related to dyspeptic symptoms and the evaluation of the quality of life was use the 8-item Short Form Health Survey in 2 categories, the physical component summary score and mental component summary score. All patients administered rabeprazole 10 mg/day for 8 weeks. We investigated the correlation between symptomatic improvement with proton pump inhibitor and quality of life. Significant symptomatic improvement was seen in the total score of 12 questions (26.7 ± 8.8 → 17.5 ± 5.9, p<0.0001), score related to reflux symptoms (14.9 ± 5.4 → 9.6 ± 3.6, p<0.0001), and score related to dyspeptic symptoms (11.8 ± 4.3 → 8.0 ± 2.9, p<0.0001). Significant improvement in quality of life was seen in the physical component summary score (47.8 ± 6.6 → 50.0 ± 5.9, p = 0.0209) and mental component summary score (47.4 ± 8.5 → 50.4 ± 5.3, p = 0.0133) with proton pump inhibitor. With proton pump inhibitor, a significant positive correlation was seen between the improvement rates in total score of 12 questions, score related to dyspeptic symptoms and in mental component summary score at 8 weeks (total score of 12 questions: r = 0.275, p = 0.0265, score related to dyspeptic symptoms: r = 0.367, p = 0.0027). In conclusion, quality of life was associated with improvement in dyspeptic symptoms with proton pump inhibitor treatment.

Introduction

The ultimate aims of pharmacological management for gastroesophageal reflux disease (GERD) are rapid symptomatic control and improved quality of life (QOL).( The results of rapid symptomatic resolution of symptoms with pharmacological management achieve greater improvements in QOL.( Accordingly, rapid symptomatic control is important in the treatment of GERD. For non-erosive reflux disease (NERD), symptom resolution within 7 days after proton pump inhibitor (PPI) treatment has been reported to correlate with the rate of symptom resolution 4 weeks later.( For reflux esophagitis (RE), symptom resolution on the first day after PPI treatment has been reported to correlate with the rate of symptom resolution 4 weeks later.( On the other hand, for functional dyspepsia (FD)( and uninvestigated dyspepsia,( the symptom resolution rate or symptomatic improvement rate after 1 week of PPI treatment reportedly do not fully predict the degree of symptomatic improvement 4 or 8 weeks later. These studies have been conducted with Western patients, however, and very few studies have examined the relationship between symptomatic improvement and QOL in Japanese GERD patients. In this study, we investigated the correlation between symptomatic improvement and QOL in Japanese GERD patients with PPI.

Methods

Patients

Eighty one Japanese outpatients with reflux and dyspeptic symptoms were enrolled between March 2008 and March 2009 (Table 1). Inclusion criteria were 20 years or older and willingness to informed consent. Patients were excluded if they had the history of gastric and duodenal ulcer, cancer and esophageal structure.

Table 1

Baseline characteristics

Age	55.7 ± 14.0
Gender (male/female)	43/38
Height (cm)	163.6 ± 7.8
Weight (kg)	61.3 ± 8.9
BMI (kg/m2)	22.8 ± 2.5
History of GERD	No history	62
	Recurrent	10
	Known	9
History of anti-acid secretion treatments (number/%)	23/27.4%
Received the life-style modification (number/%)	50/61.7%
Complicated diseases (number/%)	30/37.0%
Endoscopic findings	RE	Grade A	25
		Grade B	4
	NERD	Grade N	17
		Grade M	19
	Uninvestigated		16
Symptom score (FSSG)	Total symptom score	26.7 ± 8.8*
	Reflux symptom score	14.9 ± 5.4*
	Dyspepsia symptom score	11.8 ± 4.3*
QOL score (SF-8)	PCS	47.8 ± 6.6*
	MCS	47.4 ± 8.5*

*mean ± SD.

RE: Reflux esophagitis. NERD: Non-erosive reflux disease. PCS: physical component summary score. MCS: mental component summary score.

Symptom assessment

The reflux symptom defined as heartburn and acid regurgitation and the dyspeptic symptom defined as postprandial fullness and early satiation, mainly. These symptoms were evaluated using the Frequency Scale for the Symptom of GERD (FSSG), a questionnaire developed for use with Japanese patients( (Fig. 1). The questions of FSSG are related to the 12 symptoms that Japanese patients with GERD complain of most often, not only ’heartburn’ and ’regurgitation’, but also dyspeptic symptoms such as ’heavy stomach’ and ’feeling full quickly’.( The FSSG is designed to score the frequency at which patients experience symptoms, and has been shown to be useful in the diagnosis of GERD,( assessment of response to GERD therapy( and prediction of optimum treatment.(

Fig. 1

Frequency Scale for the Symptoms of GERD (FSSG).

The FSSG was devised from these 12 questions, which were scored to indicate the frequency of symptoms, as follows: never/0; occasionally/1; sometimes/2; often/3; and always/4. The FSSG was evaluated using the total score (F-TS), the score for the 5 questions concerning acid reflux-related symptoms (F-RS), and for the seven questions concerning dyspeptic symptoms (F-DS) as indicated in Fig. 1.

QOL assessment

We evaluated QOL in 2 categories, the physical component summary score (PCS) and mental component summary score (MCS), using the 8-item Short Form Health Survey (SF–8TM).( The mean scores for the Japanese general population are 50 points in PCS and MCS scores. A score of <50 thus indicated impaired QOL and the score of ⩾50 is considered to indicate the improved QOL.

Endoscopic findings

Endoscopy was underwent at pre-treatment and evaluated according to 2nd modified Los Angeles (LA) classification( (Grade N, no endoscopic mucosal changes; Grade M, minimal change; Grade A, one or more mucosal breaks ⩽5 mm long that do not extend between the tops of two mucosal folds; Grade B, one or more mucosal breaks >5 mm long that do not extend between the tops of two mucosal folds; Grade C, one or more mucosal breaks that are continuous between the tops of two or more mucosal folds, but do not involve the entire esophageal circumference; and Grade D, a mucosal break that involves the entire esophageal circumference) among the patients who were able to obtain agreement.

Treatment

All Patients were administered rabeprazole 10 mg/day for 8 weeks, and completed these 2 questionnaires about their symptoms and QOL at pre-treatment and after 4 and 8 weeks. All the patients had signed an informed consent. Our study was approved by our hospital Ethics Committee.

Statistical analysis

We investigated the correlation between reflux and dyspeptic symptoms and QOL at pre-PPI treatment. And we examine the relation between the improvement rates in these symptoms and in QOL with PPI. Results are expressed as mean ± SD. Continuous variables were compared using one-way factorial analysis of variance (ANOVA), and discontinuous variables using Fisher’s exact test. Correlations between variables were examined using Spearman’s correlation coefficient between ranks. The improvement of F-TS, F-RS and F-DS associated with improvement of QOL (PCS or MCS scores ⩾50) were identified by univariate logistic regression analysis. Results are presented as odds ratios with 95% confidence interval (CI). For all analyses, p<0.05 was considered to signify a significant difference. Statistical analysis was performed using SPSS ver.19 (Chicago, IL).

Results

Changes in FSSG scores and QOL (PCS and MCS) during PPI treatment

Significant symptomatic improvement was seen in the F-TS, F-RS and F-DS at each evaluation point (F-TS: pre 26.7 ± 8.8, 4 weeks 20.1 ± 6.5, p<0.0001, 8 weeks 17.5 ± 5.9, p<0.0001; F-RS: pre 14.9 ± 5.4, 4 weeks 11.1 ± 4.0, p<0.0001, 8 weeks 9.6 ± 3.6, p<0.0001; F-DS: pre 11.8 ± 4.3, 4 weeks 9.1 ± 3.2, p<0.0001, 8 weeks 8.0 ± 2.9, p<0.0001) (Fig. 2). Significant improvement in QOL was seen in both the PCS (pre 47.8 ± 6.6, 4 weeks 50.2 ± 5.2, p = 0.0015, 8 weeks 50.0 ± 5.9, p = 0.0209) and MCS (pre 47.4 ± 8.5, 4 weeks 50.6 ± 5.9, p = 0.0103, 8 weeks 50.4 ± 5.3, p = 0.0133) with treatment (Fig. 3).

Fig. 2

Changes in FSSG score at each time of assessment. Mean ± SD. FSSG: the Frequency Scale for the Symptom of GERD. *p<0.05 comparison with Pre treatment.

Fig. 3

Change rates in QOL at each time of assessment. QOL: Quality of Life. PCS: physical component summary score. MCS: mental component summary score. *p<0.05 comparison with Pre treatment. Spearman’s correlation coefficient.

Correlation between GERD symptoms and QOL at pre-treatment

At pre-treatment, QOL correlated negatively with F-TS (PCS: r = −0.0359, p = 0.0010; MCS: r = −0.356, p = 0.0011), F-RS (PCS: r = −0.0273, p = 0.0136, MCS: r = −0.249, p = 0.0253) and F-DS (PCS: r = −0.398, p = 0.0002; MCS: r = −0.422, p<0.0001) (Fig. 4).

Fig. 4

Correlation of FSSG and QOL at pre-treatment. F-TS: total score of FSSG. F-RS: acid reflux symptoms of FSSG. F-DS: dyspeptic symptoms of FSSG. QOL: Quality of Life. PCS: physical component summary score. MCS: mental component summary score. Spearman’s correlation coefficient.

Correlation between improvements in FSSG scores and QOL after 8 weeks with PPI treatment

Examination of the correlation between the improvement rate in FSSG scores and QOL after 8 weeks of treatment showed a significant positive correlation was seen between in MCS at 8 weeks and the improvement rates in F-TS (r = 0.275, p = 0.0265) and in F-DS (r = 0.367, p = 0.0027). However, No significant correlations were seen between the improvement rate in F-RS and either in PCS or in MCS (Fig. 5).

Fig. 5

Correlation of the improvements rate of FSSG and QOL after 8 weeks. F-TS: total score of FSSG. F-RS: acid reflux symptoms of FSSG. F-DS: dyspeptic symptoms of FSSG. QOL: Quality of Life. PCS: physical component summary score. MCS: mental component summary score. Spearman’s correlation coefficient.

Associated with improvement of QOL

By univariate logistic regression analysis, only improvement of F-SD was associated with improved MCS. (odds; 1.021, 95% CI; 1.001–1.041, p = 0.0391) F-TS and F-RS were not significant.

Discussion

From the report by Fujiwara et al.,( we know that the incidence of GERD has risen markedly in Japan from 1990 until now. The reasons for this trend increased gastric acid secretion in the Japanese population,( the reduced prevalence of Helicobacter pylori infection,( and obesity associated with Westernized eating habits,( Untreated GERD impairs QOL more than untreated angina pectoris or hypertension,( and the ultimate aim of GERD treatment is improved QOL.( To reverse this decline in QOL in patients with GERD, it is important to ameliorate GERD-related symptoms through treatments that prevent acid reflux.( A number of studies have identified a correlation between QOL and GERD-related symptoms. Several have indicated that GERD-related symptoms are the key to QOL, with greater Japan F-scale and SF-8 Trial (J-FAST) impairment of QOL as the severity of GERD-related symptoms increases,( greater impairment of QOL as the frequency of nocturnal GERD symptoms increases,( a correlation between the frequency of heartburn and regurgitation and impairment of QOL,( and a marked decrease in QOL with 2 or more episodes of heartburn per week.(

Our results also showed a negative correlation between the severity of both reflux and dyspeptic symptoms and QOL at pre-treatment PPI. The FSSG used in this study scores the frequency of typical GERD-related symptoms. The FSSG total score of 12 symptoms in Japanese GERD patients can also be subdivided into a score related to reflux symptoms such as heartburn and regurgitation (F-RS) and a score related to dyspeptic symptoms such as bloating and fullness (F-DS).( Greater impairment in QOL prior to PPI treatment was seen as symptom severity increased, as evidenced by the F-TS, F-RS and F-DS. Not only was a correlation seen between QOL and acid reflux symptoms, but the severity of dyspeptic symptoms also impaired QOL. This finding agrees with previous studies that suggest dyspeptic symptoms impact adversely on QOL.(

We administered rabeprazole 10 mg/day for 8 weeks, resulting in significant improvements in the F-TS, F-RS and F-DS, as well as improvement in QOL. Kusano et al.( also used the FSSG to evaluate the efficacy of 8 weeks of treatment with rabeprazole 10 mg/day. As with this study, they found that not only acid reflux symptoms, but also dyspeptic symptoms were improved, so they defined dyspeptic symptoms that respond to a PPI as ’acid related dyspepsia’.

We also examined the correlation between the improvement rate in GERD symptoms and in QOL. Earlier studies found a correlation between the rate of symptom resolution with pharmacological management and the improvement rate in QOL,( and showed that complete resolution of symptoms is required to achieve high improvements in QOL.( In our study, a significant positive correlation was seen between the improved MCS and the improvement rates in F-TS and F-DS. However, no correlations were seen between the improvement rate in F-RS and either the improvement rates in PCS or in MCS. This lack of correlation between the improvement rate in acid reflux symptoms and in PCS or MCS is extremely interesting. The reason that the severity of acid reflux symptoms, typical symptoms of GERD, correlated with QOL, but in our study, the improvement of reflux symptoms was not correlated with the improvement of QOL, is unclear. There is possibility of two reasons. First, the ratio of RE was low in our study (35.8%). Pooled response rates of PPI were significantly higher for patients with RE compared with NERD.( There is a possibility that acid reflux symptoms correlates to QOL, if there are a lot of ratios of RE. Second, it is a difference of the symptom improvement speed and the QOL improvement speed. The symptom improvement speed was prompt, and the QOL improvement speed was slow. Especially, the improvement speed of acid reflux symptoms was quickly, and the improvement speed of dyspeptic symptoms was more gradual. The improvement speed of acid reflux symptoms did not catch up at the QOL improvement speed for promptness, and the improvement speed of dyspeptic symptoms caught up oppositely at the QOL improvement speed. In a current report, the symptom resolution within 7 days after PPI treatment has been correlated with the rate of symptom resolution 4 weeks later, but not with QOL improvement.( In our study, it is thought that the improvement of dyspeptic symptoms associated in QOL improvement, importantly. The resolution rate for heartburn symptoms with PPI treatment is lower in the presence of multiple dyspeptic symptoms.( Consideration of these factors suggests that improvement in dyspeptic symptoms is a factor that strongly influences improved QOL with PPI therapy.

Study Limitation

Our study is a single arm open label study without placebo control.

Conflict of Interest

No conflict of interest has been declared by the authors.