GENETIC TESTING IMPROVES THE DIAGNOSIS OF ADULT TYPE HYPOLACTASIA IN THE MEDITERRANEAN POPULATION OF SARDINIA

Recently, the C/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia, located in Southern Europe, the C/T-13910 polymorphism may be useful or not for the diagnosis of adult type hypolactasia. DESIGN: Validation study of a genetic testing for adult type hypolactasia in Sardinians. SETTING: Brotzu Hospital and Microcitemico Hospital, Cagliari, Italy. SUBJECTS: The sample consisted in 84 Sardinian individuals (63 women and 21 men; range 20-73 years) selected from a group of 832 patients. METHODS: Genetic testing was compared to an improved test obtained by a combination of different breath hydrogen tests and clinical assessment. RESULTS: We found that all 49 individuals with lactose malabsorption, demonstrated by a combination of different breath hydrogen tests and clinical assessment, carried the C/C-13910 genotype associated with lactase non-persistence, 23 individuals with lactose normal absorption carried the C/T-13910 genotype associated with lactase persistence and only one person with the above phenotype showed a discordant C/C-13910 genotype. The genetic testing showed very high sensitivity, specificity, positive and negative predictive values of 100, 95.8, 98 and 100%, respectively. CONCLUSIONS: Sardinians, unlike some ethnic groups in sub-Saharan Africa, show the same genetic association of hypolactasia with the C/T-13910 variant as other North-European populations. The genetic testing for the C/T-13910 variant may contribute to improving the diagnosis of adult type hypolactasia

SYMPTOMS ASSOCIATED TO WEAKLY ACIDIC REFLUX AND ESOPHAGEAL MOTILITY ABNORMALITIES ARE MORE COMMON THAN FUNCTIONAL CHEST-PAIN IN PATIENTS WITH NON-CARDIAC CHEST PAIN REFRACTORY TO PPI THERAPY

INTRODUCTION: Previous studies showed that PPIs are less effective in relieving non-cardiac chest-pain (NCCP) than heartburn. Data on the potential causes of this finding are lacking. AIMS & METHODS: To assess the frequency of esophageal motility abnormalities and reflux disease in NCCP refractory patients. Consecutive NCCP refractory patients (response <50%) underwent conventional manometry and impedance-pH testing while on or off-PPI therapy. Manometric pattern was defined as follows: Normal peristalsis (NP; normal wave amplitude and progression), Ineffective Esophageal Motility (IEM; lower distal wave amplitude in 30% of wet swallows), Distal Esophageal Spasm (DES; simultaneous wave progression in >10% of wet swallows with normal/high distal amplitude), Nutcracker Esophagus (NE; normal wave progression and high distal wave amplitude). We also measured esophageal acid exposure time (AET), reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP+ if 95%) and symptom index (SI+ if 50%). RESULTS: One-hundred and fifty NCCP patients (83F/67M; mean age 48; 6% ERD/94% NERD) were enrolled. At manometry testing, 96 (64%) patients had NP, 35 (23%) had DES, 16 (11%) had NE and 3 (2%) had IEM (i.e. 54 (36%) had motor abnormalities). At impedance-pH monitoring, 50 patients were studied on- and 100 off-PPI treatment. We found 26 (17%) patients with an abnormal AET, although 10 (8%) of them were on-PPI (i.e. acid GERD). Out of the remaining 124 (83%) patients, 16 (11%) had a positive SAP/SI to acid reflux (i.e. hypersensitive esophagus to acid), 41 (28%) to weakly acidic reflux (i.e. weakly acidic GERD) and 14 (9%) to both acid and weakly acidic reflux (i.e. mixed GERD). Fifty-three (35%) patients had no association between reflux and symptoms and out of them 34 (23%) had NP (i.e. functional chest-pain patients). CONCLUSION: Symptoms related to weakly acidic reflux and motility abnormalities are very common in NCCP refractory patients and may be responsible for the persistence of symptoms in the majority of them. A “functional” disorder may account for a quarter of these patients. Notably, an incomplete acid suppression may be responsible of poor response in a consistent group of patients

IMPEDANCE-PH MONITORING AND SYMPTOM ANALYSIS IN EROSIVE AND NON-EROSIVE REFLUX DISEASE PATIENTS WITH NON-CARDIAC CHEST PAIN − A STUDY ON AND OFF THERAPY

INTRODUCTION: The aetiology of non-cardiac chest-pain (NCCP) is unknown, but previous studies demonstrated that both visceral hyperalgesia to esophageal distension or even chemostimulation with acid reflux (AR) are frequently involved. However, the role of weakly acidic reflux (WAR) in provoking NCCP is poorly known AIMS & METHODS: To assess the role of WAR in a large group of NCCP patients studied using multichannel intraluminal impedance-pH (MII-pH). Consecutive patients complaining of NCCP were studied while on or off-PPI therapy (discontinued PPI >14 days prior to test). They referred to our units for undergoing pre-operative evaluation or in order to be studied due to PPI refractoriness. After upper endoscopy, patients were classified as having erosive reflux disease (ERD), in case of esophageal mucosal breaks, or non-erosive reflux disease (NERD). During MII-pH tracings analysis we measured esophageal acid exposure time (AET), characteristics of reflux episodes (AR/WAR) and symptom-reflux association using both symptom association probability (SAP+ if95%) and symptom index (SI+ if50%). Symptom association was considered positive in case of SAP+ and/or SI+. RESULTS: Out of 354 NCCP patients, 301 (85%) experienced NCCP during the MIIpH test and were further analyzed. Among the 231 off-PPI (127F/104M, mean age 48; 11% ERD/89% NERD), 70 (30%) had an abnormal AET. Out of 161 (70%) with normal AET, a positive SAP/SI was found in 39 (16%) for AR, 23 (10%) for both AR and WAR and 30 (13%) for WAR. Seventy-two patients (31%) patients had no refluxsymptom association. In the group of patients on-PPI (N = 70; 36F/34M, mean age 50; 9% ERD/91% NERD), 9 (13%) had an abnormal AET. Out of 61 (87%) with normal AET, 7 (10%) had a positive SAP for AR, 24 (34%) for WAR and 4 (6%) for both AR and WAR. Twenty-six (37%) patients had no reflux-symptom association. Identifying patients with symptomatic WAR reduces the number of patients with unexplained NCCP from 102 (44%) to 72 (31%) and from 50 (71%) to 28 (37%) among patients off-PPI and on-PPI, respectively (p<0.01). CONCLUSION: Our data emphasize the important role of WAR in provoking NCCP, in particular in patients on acid-suppressive therapy. This further supports the use of MII-pH in the diagnostic algorithm of unexplained chest pain

Symptoms associated to weakly acidic reflux and esophageal motility abnormalities are common findings in patients with Non-Cardiac Chest Pain non-responding to PPI therapy. A multicenter italian study

Introduction: Previous studies showed that both visceral hyperalgesia to esophageal distension or even chemostimulation provoked by gastro-esophageal reflux and esophageal motor dysfunction are frequently involved in the aetiology of non-cardiac chest-pain (NCCP). Moreover, proton pump inhibitor (PPI) therapy has been demonstrated to be less effective on symptom relief in NCCP patients than in those with heartburn. Data on the potential causes of this reduced response rate are lacking. Aim: To assess the frequency of esophageal motility abnormalities and reflux disease in NCCP non-responders patients. Methods: Consecutive NCCP patients non-responders to PPI (<50% symptom improvement at double doses) underwent conventional manometry and impedance-pH testing (MII-pH) while on or off-PPI therapy. Manometric pattern was defined as follows: Normal peristalsis (NP; normal wave amplitude and progression), Ineffective Esophageal Motility (IEM; lower distal wave amplitude in ≥30% of wet swallows), Distal Esophageal Spasm (DES; simultaneous wave progression in >10% of wet swallows with normal or high distal amplitude), Nutcracker Esophagus (NE; normal wave progression and high distal wave amplitude). We also measured distal esophageal acid exposure time (AET; % pH<4), reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP + if ≥ 95%) and symptom index (SI + if ≥ 50%). Results: Ninety-seven NCCP patients (55F/ 42M, mean age 48) reporting chest-pain during the testing day were enrolled. At manometry testing, NP was found in 62 (64%) patients, 23 (24%) had DES, 9 (9%) had NE and 3 (3%) had IEM. As to impedance-pH monitoring, 44 patients were studied on- and 53 off- PPI treatment. We found 13 (13%) patients with an abnormal AET, although 4 (4%) of them were on-therapy. Out of the remaining 84 (87%) patients, 8 (8%) had a positive SAP/ SI to acid reflux only, 31 (32%) to weakly acidic reflux only and 11 (11%) to both acid and weakly acidic reflux (4 were positive considering both refluxes as a whole). Thirty-four (35%) patients had no association between reflux and symptoms and out of them 23 (23%) had NP (i.e. functional chest-pain patients). Thus, at manometry testing 35 (36%) patients had esophageal motility abnormalities, while at impedance-pH monitoring 13 (13%) had acid GERD, 8 (8%) had SI/SAP+ to acid (i.e. hypersensitive esophagus to acid), 31 (32%) had SI/SAP+ to weakly acidic (i.e. weakly acidic GERD) and 11 (11%) had SI/SAP+ to both reflux (i.e. mixed GERD). Conclusion: Symptoms related to weakly acidic reflux and esophageal motility abnormalities are very common in NCCP patients non-responding to PPI therapy and may be responsible for the persistence of symptoms in the majority of these patients. The impact of this findings on NCCP management remains to be investigated by outcome studies

SYMPTOMS ASSOCIATED TOWEAKLY ACIDIC REFLUX AND ESOPHAGEAL MOTILITY ABNORMALITIES ARE COMMON FINDINGS IN PATIENTS WITH NCCP NON-RESPONDING TO PPI THERAPY

none18Background and aim: Proton pump inhibitor (PPI) therapy has been demonstrated to be less effective on symptom relief in patients with non-cardiac chest-pain (NCCP) than in those with heartburn. Data on the potential causes of this reduced response rate are lacking. Aim: To assess the frequency of esophageal motility abnormalities and reflux disease in NCCP non-responders patients. Material and methods: Consecutive NCCP patients non-responders to PPI (<50%) underwent manometry and impedance-pH testing (MII-pH) while on or off-therapy. Manometric pattern was defined according to international criteria as Normal peristalsis (NP), Ineffective Esophageal Motility (IEM), Distal Esophageal Spasm (DES), Nutcracker Esophagus (NE).We also measured esophageal acid exposure time (AET; % pH<4), reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP+ if = 95%) and symptom index (SI+ if = 50%). Results: Ninety-seven NCCP patients (55F/42M) were enrolled. At manometry testing, NP was found in 62 (64%) patients, 23 (24%) had DES, 9 (9%) had NE and 3 (3%) had IEM. As to MII-pH monitoring (44 on- and 53 patients off-PPI), we found 13 (13%) patients with an abnormal AET, although 4 (4%) of them were on-PPI. Out of the remaining 84 (87%) patients, 8 (8%) had a positive SAP/SI to acid reflux only, 31 (32%) to weakly acidic reflux only and 11 (11%) to both acid and weakly acidic reflux (4 patient were positive considering both refluxes as a whole). Thirty-four (35%) patients had no association between reflux and symptoms and out of them 23 (23%) had NP (i.e. functional chest-pain). Thus, at manometry testing 35 (36%) patients had esophageal motility abnormalities, while at MII-pH monitoring 13 (13%) had acid GERD, 8 (8%) had SI/SAP+ to acid (i.e. hypersensitive esophagus to acid), 31 (32%) had SI/SAP+ to weakly acidic (i.e. weakly acidic GERD) and 11 (11%) had SI/SAP+ to both reflux (i.e. mixed GERD). Conclusions: Symptoms related to weakly acidic reflux and esophageal motility abnormalities are very common in NCCP patients non-responding to PPI therapy and may be responsible for the persistence of symptoms in the majority of these patients.noneSavarino E.; Zentilin P.; Lo Cuoco D.; Frazzoni M.; De Bortoli N.; Martinucci I.; Casini V.; Pace F.; Barbera R.; Bergonzi M.; Di Stefano M.; Oppia F.; Usai Satta P.; Ricci G.; De Bona M.; De Boni M.; Sturniolo G.C.; Savarino V.Savarino, E.; Zentilin, P.; Lo Cuoco, D.; Frazzoni, M.; De Bortoli, N.; Martinucci, I.; Casini, V.; Pace, F.; Barbera, R.; Bergonzi, M.; Di Stefano, M.; Oppia, F.; Usai Satta, P.; Ricci, Giorgio; De Bona, M.; De Boni, M.; Sturniolo, G. C.; Savarino, V

IMPEDANCE-PH MONITORING AND SYMPTOMANALYSIS IN NON-CARDIAC CHEST PAIN PATIENTS ON AND OFF THERAPY

none18Background and aim: The aetiology of non-cardiac chest-pain (NCCP) is unknown, but previous studies demonstrated that both visceral hyperalgesia to esophageal distension or even chemostimulation with acid are frequently involved. However, the role of weakly acidic reflux in provoking NCCP is poorly known. To assess the role of weakly acidic reflux in a large group of NCCP patients studied using impedance-pH. Material and methods: Consecutive patients complaining of NCCP underwent impedance-pH monitoring while on or off-PPI therapy (discontinued PPI >14 days prior to testing). Forty-eight healthy volunteers (27F; mean age 42yrs) served as controls. During impedance-pH tracings analysis we measured distal esophageal acid exposure time, characteristics of reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP + if = 95%) and symptom index (SI + if = 50%). Symptom association was considered positive in case of SAP + and/or SI +. Results: Out of 307 NCCP patients (167F/140M, mean age 49), 266 (86%) experienced NCCP during the impedance-pH monitoring and were included in the study. Among the 198 off-PPI (111F/87M, mean age 47), a positive SAP/SI was found in 77 (39%) for acid reflux only, 31 (16%) for both acid and weakly acidic reflux and 26 (13%) for weakly acidic reflux only. Sixty-four patients (32%) patients had no reflux-symptom association. In the group of patients on-PPI (N=68; 36F/32M, mean age 50), 13 (19%) had a positive SAP for acid reflux only, 22 (32%) for weakly acidic reflux only and 5 (7%) for both acid and weakly acidic reflux. Twenty-eight (41%) patients had no reflux-symptom association. Identifying patients with symptomatic weakly acidic reflux reduces the number of patients with unexplained chest pain from 91 (46%) to 64 (32%) and from 51 (75%) to 28 (41%) among patients off-PPI and on-PPI, respectively (p<0.01). Conclusions: Monitoring for weakly acidic reflux in NCCP patients increases our ability to identify patients in whom symptoms are associated with reflux, mainly in patients on-PPI therapy. Our data support the use of ambulatory impedance-pH monitoring in a diagnostic algorithm for patients with unexplained chest pain. The impact of this improved diagnostic value on NCCP management remains to be investigated by outcome studies.noneSavarino E.; Zentilin P.; Lo Cuoco D.; Frazzoni M.; Martinucci I.; De Bortoli N.; Casini V.; Pace F.; Barbera R.; Bergonzi M.; Di Stefano M.; Oppia F.; Usai Satta P.; Ricci G.; De BonA M.; De Boni M.; Sturniolo G.C.; Savarino V.Savarino, E.; Zentilin, P.; Lo Cuoco, D.; Frazzoni, M.; Martinucci, I.; De Bortoli, N.; Casini, V.; Pace, F.; Barbera, R.; Bergonzi, M.; Di Stefano, M.; Oppia, F.; Usai Satta, P.; Ricci, Giorgio; De BonA, M.; De Boni, M.; Sturniolo, G. C.; Savarino, V