Introduction
Esophageal reflux burden can be quantified using acid exposure time (AET), mean nocturnal baseline impedance (MNBI) and numbers of reflux episodes (RE), each of which has identified thresholds for physiologic, borderline and pathologic reflux evidence. Alternate parameters such as reflux-symptom association on ambulatory reflux monitoring, hiatus hernia on high resolution manometry, and advanced esophagitis grade on endoscopy escalate confidence for reflux. Each of these parameters has varying importance in determining conclusive evidence of gastroesophageal reflux disease (GERD).
Aims & Methods
Our aim was to determine if a novel reflux score (the Lyon Score) designed to quantify reflux burden can phenotype reflux syndromes and predict treatment outcome from medical or surgical anti-reflux therapy. Scores and ranges were assigned a priori to thresholds for each metric based on available research, the Lyon Consensus and ROME phenotypes (Table). An existing database of endoscopy-negative patients with typical reflux symptoms (heartburn, regurgitation, chest pain) evaluated off therapy for persisting reflux symptoms were reviewed from two centers (one each in Europe and US). Included patients were required to have completed high resolution manometry (Medtronic, Duluth, GA) and ambulatory pH-impedance monitoring (Diversatek, Boulder, CO) off antisecretory therapy. Symptom response was assessed using change in global symptom scores from validated symptom questionnaires over follow-up; a 50% reduction in global symptoms constituted a response to anti-reflux therapy, both medical management and anti-reflux surgery. Receiver operating characteristics (ROC) analysis determined performance of the scoring system in predicting overall response as well as within each distinct syndrome, and principal component analysis identified predictors of response within the scoring system.
Results
Data from 281 patients (median age 53 yr, 57.7% female) was analyzed, 71.9% with heartburn, 13.9% with regurgitation and 14.3% with chest pain. The median Lyon score was 4.0 (IQR 1.5-8.0, range 0.0-16.0). On ROC analysis, the Lyon score demonstrated an AUC of 0.816 in predicting 50% symptom improvement (p=0.026), with an optimal Lyon score threshold of 3.75 (sensitivity 81.2%, specificity 74.1%). The Lyon score performed better than any of the individual components of the score, and only AET (AUC 0.770, p=0.029), MNBI (AUC 0.747, p=0.030) and RE (AUC 0.728, p=0.030) approached the combined score. Using the Lyon score, patients were successfully phenotyped into distinct syndromes (Table), whereby proportions of patients with 50% response from anti-reflux therapy progressively increased across phenotypes with increasing reflux evidence: idiopathic heartburn: 6.1%, isolated permeability defect: 18.2%, reflux hypersensitivity: 27.7%, borderline GERD: 55.9%, conclusive GERD 76.6%, severe GERD 76.9% (Table, p<0.001 across groups). On principal component analysis, AET, MNBI and RE all demonstrated high values within the component matrix (≥0.80 for each), suggesting that each of these primary metrics carries independent weight in driving response to anti-reflux therapy.
| Phenotype, score range | No GERD* (0-0.5) | Isolated permeability defect
(0.5-2.0) | Reflux hypersensitivity (1.0-3.0) | Inconclusive or borderline GERD (≥3.0) | Conclusive GERD (≥5.0) | Severe GERD (≥10.0) |
| EGD | Normal: 0
LA A: 0.5 | Normal-0
LA A: 0.5 | Normal-0
LA A: 0.5 | Normal- 0 LA A: 0.5 | LA B: 5 | LA C/D: 10 |
| AET | < 4.0%: 0 | < 4.0%: 0
| < 4.0%: 0
| 4-6%: 2 | >6.0%: 5 | >10%: 10 |
| RE (number) | <40: 0 | <40: 0
40-80: 1 | <40: 0
40-80:1 | <40: 0
40-80: 1
>80: 2 | <40: 0
40-80: 1
>80: 2 | <40: 0
40-80: 1
>80: 2 |
| MNBI (ohms) | >2500: 0 | <1500: 1 | <1500:1
1500-2499: 0.5
>2500: 0 | <1500: 1
1500-2499 0.5
>2500- 0 | < 1500: 1
1500-2499: 0.5
>2500: 0 | <1500: 1
1500-2499: 0.5
>2500: 0 |
| RSA | Negative: 0 | Negative: 0 | Positive:1 | NA | Negative: 0
Positive: 1 | Negative:0
Positive: 1 |
| Hiatus Hernia | Negative: 0 | Negative: 0 | Negative: 0
<3 cm: 1
≥3 cm: 2 | Negative-0
<3 cm: 1
≥3 cm: 2 | Negative: 0
<3 cm: 1
≥3 cm: 2 | Negative: 0
<3 cm: 1
≥3 cm: 2 |
| Median score (IQR) | 0.0 (0.0-0.0) | 2.0 (1.0-2.0) | 1.4 (0.5-2.3) | 4.3 (2.8-4.7) | 6.5 (5.5-8.0) | 14.0 (12.0-15.0) |
| 50% response** | 3/49 (6.1%) | 4/22 (18.2%) | 13/47 (27.7%) | 19/34 (55.9%) | 59/77 (76.6%) | 40/52 (76.9%) |
GERD: gastroesophageal reflux disease; EGD: esophagogastroduodenoscopy; LA: Los Angeles grades (A/B/C/D); AET: acid exposure time; RE: reflux episodes: MNBI: mean nocturnal baseline impedance: RSA: reflux symptom association; IQR: interquartile range
*idiopathic heartburn, presumed esophageal chest pain; **improvement with medical or surgical anti-reflux therapy;
Conclusion
The novel Lyon score segregates reflux phenotypes, and identifies likelihood of symptom response from anti-reflux therapy. Prospective validation of the Lyon score is warranted.
