The Results From Up-Front Esophageal Testing Predict Proton Pump Inhibitor Response in Patients With Chronic Cough

Abstract

INTRODUCTION: The clinical management of chronic cough patients is challenging, and their response to proton pump inhibitors (PPIs) is considered as unsatisfactory. Few data concerning the association between impedance-pH variables and PPI response in these patients are available. Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index increase the diagnostic yield of impedance-pH in gastroesophageal reflux disease. METHODS: Demographic, clinical, and endoscopy findings; impedance-pH; and high-resolution manometry tracings from consecutive patients assessed for cough were evaluated. Univariable and multivariable regression models were generated to evaluate the association between impedance-pH and high-resolution manometry findings, endoscopic and clinical characteristics, and PPI response. RESULTS: A total of 178 patients were included. Eighty-four of 178 cough patients (47.2%) displayed grade C-D erosive esophagitis or were characterized by a pathological acid exposure time (AET) and/or positive symptom association probability/symptom index. When also considering MNBI and PSPW, 135 of 178 patients (75.8%) were characterized by the evidence of reflux disease (P < 0.001). Eighty patients (44.9%) had cough responding to PPIs, whereas 98 (55.1%) were nonresponders (P = 0.071). At the receiver operating characteristic analysis, both PSPW index and MNBI were associated to PPI responsiveness. MNBI and PSPW index showed higher sensitivity in predicting PPI response compared with AET and symptom association probability/symptom index. The area under the curves of MNBI and PSPW index were significantly higher than that of AET (P < 0.01 for both comparisons). When patients were stratified according to AET and excluding those with erosive esophagitis, pathological MNBI or PSPW index, hiatal hernia, and hypomotility features were associated to PPI response in all groups. DISCUSSION: Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response.

Applying Lyon Consensus criteria in the work‐up of patients with proton pump inhibitory‐refractory heartburn

“…This result, achieved off‐therapy in the clinical setting of PPI refractoriness, confirms recent findings showing that assessment of impedance metrics combined with an appraisal of Lyon‐defined AET thresholds increases the diagnostic yield of reflux monitoring 15 . It could be argued that recently defined threshold values 15 adopted in the present study for new impedance metrics, namely PSPW index and MNBI, are at variance with those previously defined 11 and validated in several subsequent studies 13,14,19,26‐30 ; however, the variance was only minor and would have not influenced our present findings. Moreover, considering that there is some variability even among expert observers in differentiating true reflux from artifact on impedance‐pH tracings 31 and that PSPW assessment depends on accurate identification of reflux episodes, we keep on considering only concomitant positivity of PSPW index and MNBI as reliable for diagnostic purposes, as previously suggested 11,13‐15,19 …”

“…Therefore, we focused our attention on impedance metrics, namely total reflux episodes, PSPW index, and MNBI adopting the recently defined threshold values. 15 Total reflux episodes represent reflux burden comprising acid and weakly acidic refluxes, the latter constituting the majority of reflux events during PPI therapy 13,20 ; of note, the value of 40 as the physiological threshold adopted in the present study is the same proposed by the Lyon Consensus for total reflux episodes [11][12][13][14][15]19,20 Concomitant positivity of PSPW index and MNBI was found to link heartburn 11,14,19 and chronic cough 26 with reflux better than AET. In our recent large multicentre study performed in PPI-dependent heartburn patients, 15 concomitant positivity of PSPW index and MNBI was significantly higher in cases with inconclusive than in those with normal AET as defined accordingly to Lyon Consensus.…”

“…MNBI represents mucosal integrity, low values being directly related to the impairment of chemical clearance as shown by concomitant low values of PSPW index 11‐15,19,20 . Concomitant positivity of PSPW index and MNBI was found to link heartburn 11,14,19 and chronic cough 26 with reflux better than AET. In our recent large multicentre study performed in PPI‐dependent heartburn patients, 15 concomitant positivity of PSPW index and MNBI was significantly higher in cases with inconclusive than in those with normal AET as defined accordingly to Lyon Consensus 5 …”

Association between post‐reflux swallow‐induced peristaltic wave index and esophageal mucosal integrity in patients with GERD symptoms

“…These results suggest that the proposed AET cut-off >6% is highly specific but sensitivity is only moderate and assessment of MNBI and PSPW index allows to better identify GERD cases, according to recent findings. 35,36 We adopted a 2292Ω threshold for MNBI according to published outcome studies [9][10][11][12][13][14]35,36,39 ; recently, a slightly different threshold value (2000Ω) has been proposed, 31 which significantly increases the diagnostic yield of MII-pH monitoring in patients with inconclusive AET when combined with a 50% PSPW index cut-off. 31 As far as we know, this is the first study aimed at thorough evaluation of the potential relationship between PSPW index and mucosal integrity in patients with typical GERD symptoms.…”

Efficacy of laparoscopic fundoplication in patients with chronic cough and gastro-oesophageal reflux

“…However, their role in determining whether GORD is responsible for laryngopharyngeal symptoms is still evolving [ 26 ]. A combination of oesophageal physiology metrics such as acid exposure time and symptom association score may be the best way to predict response of cough to proton-pump inhibitor [ 27 , 28 ], which presumably would extrapolate to the efficacy of anti-reflux surgery.…”