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Differences in Motility and Reflux Profiles on Esophageal Function Testing Between Upper and Lower Airway Manifestations of Gastroesophageal Reflux Disease
Sa1172
Background: Idiopathic pulmonary fibrosis (IPF) is a universally fatal lung disease with limited medical therapeutic options. Gastroesophageal reflux disease (GERD) has been shown to be a putative risk factor in the pathogenesis of IPF, although the mechanism is poorly understood. Current guidelines from the American Thoracic Society suggest the conditional use of proton pump inhibition (PPI) for the management of IPF patients. However, there is a lack of strong evidence to support this recommendation, as prior studies have demonstrated mixed results. Aim: To perform a meta-analysis and systematic review of existing literature on the effect of PPI on survival and other clinical outcomes in IPF patients. Methods: Clinical studies of adult patients with IPF with data comparing mortality of PPI users versus non-users were identified using MEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through November 2016. Two reviewers independently extracted data on study characteristics and outcomes. For the meta-analysis, the primary metameter was the hazard ratio (HR) for survival among PPI users versus non-users. Random effects model was used due to anticipated heterogeneity. Additional outcomes reviewed included change in pulmonary function, 6-minute walk distance, and hospital readmission rates. Results: Five studies (n=3742) met inclusion criteria. The pooled HR in PPI users versus nonusers was 0.74 (95% Confidence Interval: 0.40, 1.39). No significant single large study or temporal effect was seen. Only one study reported additional pulmonary outcomes, and none were impacted by PPI use. Significant heterogeneity of studies was noted (Figure 1). Conclusions: PPI use was not associated with statistically significant increase in survival in IPF patients, although a trend towards improved survival was noted. PPI therapy solely targets acid rather than bolus reflux which may explain this finding. Additionally, the significant heterogeneity across studies likely contributes to confounding. However, based on this data, universal PPI use in IPF patients with the goal to improve pulmonary and survival outcomes does not seem to be supported. Future studies should aim to better understand the pathophysiology of GERD and the potential role of PPI therapy in IPF to help guide management of this difficult patient population.
Figure 2
Sa1171 DIFFERENCES IN MOTILITY AND REFLUX PROFILES ON ESOPHAGEAL FUNCTION TESTING BETWEEN UPPER AND LOWER AIRWAY MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE Wai-Kit Lo, Lawrence F. Borges, Kelly Hathorn, Thomas L. Carroll, Hilary J. Goldberg, Robert Burakoff, Natan Feldman, Walter W. Chan Background: Gastroesophageal reflux disease (GERD) may present with extra-esophageal manifestations involving the upper airway [laryngo-pharyngeal reflux (LPR)] and lower airway [chronic lung disease (CLD)]. While some clinical symptoms may overlap, the consequences of lower airway reflux are more severe and may suggest a different pattern/ severity of reflux involvement. The esophageal function and reflux profiles of upper vs lower airway symptoms on objective testing are currently unclear, but may help understand the pathophysiology of extra-esophageal manifestations of GERD and guide further management. Aim: To compare the esophageal function and reflux profiles of LPR and CLD patients undergoing high resolution esophageal manometry (HRM) and multichannel intraluminal impedance and pH testing (MII-pH) for assessment of symptoms. Methods: This was a retrospective cohort study of patients with LPR symptoms or CLD (excluding autoimmune etiologies) who underwent HRM and MII-pH off acid suppression at a tertiary center since 2008. Patients with prior antireflux surgery were excluded. Patient demographics, clinical history, and HRM/MII-pH findings were reviewed. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between LPR and CLD groups. Results: 149 subjects (53% LPR vs 47% CLD, 45% male, mean age at testing: 56) met inclusion criteria for the study. Compared to LPR patients, CLD subjects presenting for esophageal function testing were more likely to be male (61.4% vs 30.3%, p=0.0002) and demonstrated more severe reflux parameters, including abnormal acid exposure time (24.3% vs 8.4%, p=0.01), total reflux episodes (59.9 vs 45.1, p=0.008), and proximal acid reflux episodes (13.7 vs 3.14, p<0.0001). The mean nocturnal baseline impedance, a novel measure of esophageal mucosal integrity, was also lower in the CLD group (1927.5 ohms vs 2441.4 ohms), suggesting more severe reflux, although statistical significance was not reached. Higher proportion of weak swallows, defined as distal contractile integral 100-450 mmHg.cm.s, were noted on HRM among CLD patients compared to the LPR group (18% vs 5.88%, p=0.03). Conclusion: In a cohort of patients with LPR symptoms or CLD undergoing esophageal function testing, male gender, abnormal parameters of acid reflux on MII-pH, and weak swallows on HRM were significantly more prevalent in patients with CLD compared to LPR. Reflux and its consequences may be more prevalent and more severe in lower airway manifestations of GERD compared to upper airway symptoms. Earlier esophageal function testing and reflux intervention may be indicated in patients with suspected lower airway manifestations of GERD. Future studies should focus on the role of reflux and esophageal function testing in guiding clinical management in this population.
Figure 1. Forest plot of all included studies demonstrating trend towards improved survival with PPI use in IPF patients.
Sa1173 FEMALE GENDER IS THE ONLY SIGNIFICANT CLINICAL PREDICTOR FOR ABNORMAL PHARYNGEAL REFLUX ON IMPEDANCE-PH MONITORING IN PATIENTS WITH SUSPECTED LARYNGOPHARYNGEAL REFLUX SYMPTOMS Kelly Hathorn, Lawrence F. Borges, Thomas L. Carroll, Natan Feldman, Walter W. Chan Background: Patients with suspected laryngopharyngeal reflux (LPR) symptoms pose a diagnostic challenge, as traditional reflux testing modalities have been inconsistent in identifying patients who may respond to anti-reflux therapy. Modified multichannel intraluminal impedance and pH (MII-pH) catheters with additional impedance electrode pairs in the hypopharynx have been developed to better identify full-column reflux events affecting the pharynx. Despite the new technologies, little is known about the demographic and clinical characteristics associated with increased risk of abnormal pharyngeal reflux events. A better understanding of the patient factors influencing risk of frequent pharyngeal events may improve our ability to diagnose and manage LPR. Aim: To determine demographic or clinical factors that are associated with increased pharyngeal reflux events in patients with suspected LPR. Methods: This was a retrospective cohort study of adults with suspected LPR who underwent MII-pH with additional pharyngeal impedance channels from 4/2015 to 10/ 2016. Demographic and clinical information were collected for each patient, including age, gender, BMI, smoking history, history of esophageal reflux symptoms, and medication use. Forward stepwise logistic regression was used to identify significant predictive factors for abnormal pharyngeal reflux (defined as ≥ 2 pharyngeal impedance events / 24 hours). Results: 60 subjects (mean age = 55.5 yrs, 71.7% female) met criteria for inclusion. 17 (28.3%) were tested while on proton pump inhibitors. Overall, 39 subjects (65%) were found to have abnormal pharyngeal reflux on impedance. Of them, 30 (76.9%) were women, mean BMI was 27.5+/-5.6, 12 (30.8%) were former smokers, and 3 (7.7%) had a history of narcotic or benzodiazepine use. On multivariate analysis, female gender (OR 6.29, p= 0.04) was the only factor that remained significantly associated with abnormal pharyngeal reflux, after controlling for potential confounders. Conclusion: Among patients with suspected LPR symptoms undergoing MII-pH with pharyngeal impedance channels, female gender was the only independent positive predictor for abnormal pharyngeal reflux events. Whether this represents a true increase in LPR prevalence among female patients, or different
Table 1. Demographics, MII-pH, and HREM parameters that may help distinguish LPR from CLD. Missing data in some patients may alter the N in the denominator, as specified in the table. MII-pH = multichannel intraluminal impedance and pH; HREM = high resolution esophageal manometry; LPR = laryngopharyngeal reflux; CLD = chronic lung disease; AET = acid exposure time; SD = standard deviation; NS = not significant.
S-243
AGA Abstracts
AGA Abstracts
EFFECT OF PROTON PUMP INHIBITION ON SURVIVAL IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: A META-ANALYSIS AND SYSTEMATIC REVIEW Sravanya Gavini, Wai-Kit Lo, Lawrence F. Borges, Alison Goldin, Walter W. Chan
Background: Idiopathic pulmonary fibrosis (IPF) is a universally fatal lung disease with limited medical therapeutic options. Gastroesophageal reflux disease (GERD) has been shown to be a putative risk factor in the pathogenesis of IPF, although the mechanism is poorly understood. Current guidelines from the American Thoracic Society suggest the conditional use of proton pump inhibition (PPI) for the management of IPF patients. However, there is a lack of strong evidence to support this recommendation, as prior studies have demonstrated mixed results. Aim: To perform a meta-analysis and systematic review of existing literature on the effect of PPI on survival and other clinical outcomes in IPF patients. Methods: Clinical studies of adult patients with IPF with data comparing mortality of PPI users versus non-users were identified using MEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through November 2016. Two reviewers independently extracted data on study characteristics and outcomes. For the meta-analysis, the primary metameter was the hazard ratio (HR) for survival among PPI users versus non-users. Random effects model was used due to anticipated heterogeneity. Additional outcomes reviewed included change in pulmonary function, 6-minute walk distance, and hospital readmission rates. Results: Five studies (n=3742) met inclusion criteria. The pooled HR in PPI users versus nonusers was 0.74 (95% Confidence Interval: 0.40, 1.39). No significant single large study or temporal effect was seen. Only one study reported additional pulmonary outcomes, and none were impacted by PPI use. Significant heterogeneity of studies was noted (Figure 1). Conclusions: PPI use was not associated with statistically significant increase in survival in IPF patients, although a trend towards improved survival was noted. PPI therapy solely targets acid rather than bolus reflux which may explain this finding. Additionally, the significant heterogeneity across studies likely contributes to confounding. However, based on this data, universal PPI use in IPF patients with the goal to improve pulmonary and survival outcomes does not seem to be supported. Future studies should aim to better understand the pathophysiology of GERD and the potential role of PPI therapy in IPF to help guide management of this difficult patient population.
Figure 2
Sa1171 DIFFERENCES IN MOTILITY AND REFLUX PROFILES ON ESOPHAGEAL FUNCTION TESTING BETWEEN UPPER AND LOWER AIRWAY MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE Wai-Kit Lo, Lawrence F. Borges, Kelly Hathorn, Thomas L. Carroll, Hilary J. Goldberg, Robert Burakoff, Natan Feldman, Walter W. Chan Background: Gastroesophageal reflux disease (GERD) may present with extra-esophageal manifestations involving the upper airway [laryngo-pharyngeal reflux (LPR)] and lower airway [chronic lung disease (CLD)]. While some clinical symptoms may overlap, the consequences of lower airway reflux are more severe and may suggest a different pattern/ severity of reflux involvement. The esophageal function and reflux profiles of upper vs lower airway symptoms on objective testing are currently unclear, but may help understand the pathophysiology of extra-esophageal manifestations of GERD and guide further management. Aim: To compare the esophageal function and reflux profiles of LPR and CLD patients undergoing high resolution esophageal manometry (HRM) and multichannel intraluminal impedance and pH testing (MII-pH) for assessment of symptoms. Methods: This was a retrospective cohort study of patients with LPR symptoms or CLD (excluding autoimmune etiologies) who underwent HRM and MII-pH off acid suppression at a tertiary center since 2008. Patients with prior antireflux surgery were excluded. Patient demographics, clinical history, and HRM/MII-pH findings were reviewed. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between LPR and CLD groups. Results: 149 subjects (53% LPR vs 47% CLD, 45% male, mean age at testing: 56) met inclusion criteria for the study. Compared to LPR patients, CLD subjects presenting for esophageal function testing were more likely to be male (61.4% vs 30.3%, p=0.0002) and demonstrated more severe reflux parameters, including abnormal acid exposure time (24.3% vs 8.4%, p=0.01), total reflux episodes (59.9 vs 45.1, p=0.008), and proximal acid reflux episodes (13.7 vs 3.14, p<0.0001). The mean nocturnal baseline impedance, a novel measure of esophageal mucosal integrity, was also lower in the CLD group (1927.5 ohms vs 2441.4 ohms), suggesting more severe reflux, although statistical significance was not reached. Higher proportion of weak swallows, defined as distal contractile integral 100-450 mmHg.cm.s, were noted on HRM among CLD patients compared to the LPR group (18% vs 5.88%, p=0.03). Conclusion: In a cohort of patients with LPR symptoms or CLD undergoing esophageal function testing, male gender, abnormal parameters of acid reflux on MII-pH, and weak swallows on HRM were significantly more prevalent in patients with CLD compared to LPR. Reflux and its consequences may be more prevalent and more severe in lower airway manifestations of GERD compared to upper airway symptoms. Earlier esophageal function testing and reflux intervention may be indicated in patients with suspected lower airway manifestations of GERD. Future studies should focus on the role of reflux and esophageal function testing in guiding clinical management in this population.
Figure 1. Forest plot of all included studies demonstrating trend towards improved survival with PPI use in IPF patients.
Sa1173 FEMALE GENDER IS THE ONLY SIGNIFICANT CLINICAL PREDICTOR FOR ABNORMAL PHARYNGEAL REFLUX ON IMPEDANCE-PH MONITORING IN PATIENTS WITH SUSPECTED LARYNGOPHARYNGEAL REFLUX SYMPTOMS Kelly Hathorn, Lawrence F. Borges, Thomas L. Carroll, Natan Feldman, Walter W. Chan Background: Patients with suspected laryngopharyngeal reflux (LPR) symptoms pose a diagnostic challenge, as traditional reflux testing modalities have been inconsistent in identifying patients who may respond to anti-reflux therapy. Modified multichannel intraluminal impedance and pH (MII-pH) catheters with additional impedance electrode pairs in the hypopharynx have been developed to better identify full-column reflux events affecting the pharynx. Despite the new technologies, little is known about the demographic and clinical characteristics associated with increased risk of abnormal pharyngeal reflux events. A better understanding of the patient factors influencing risk of frequent pharyngeal events may improve our ability to diagnose and manage LPR. Aim: To determine demographic or clinical factors that are associated with increased pharyngeal reflux events in patients with suspected LPR. Methods: This was a retrospective cohort study of adults with suspected LPR who underwent MII-pH with additional pharyngeal impedance channels from 4/2015 to 10/ 2016. Demographic and clinical information were collected for each patient, including age, gender, BMI, smoking history, history of esophageal reflux symptoms, and medication use. Forward stepwise logistic regression was used to identify significant predictive factors for abnormal pharyngeal reflux (defined as ≥ 2 pharyngeal impedance events / 24 hours). Results: 60 subjects (mean age = 55.5 yrs, 71.7% female) met criteria for inclusion. 17 (28.3%) were tested while on proton pump inhibitors. Overall, 39 subjects (65%) were found to have abnormal pharyngeal reflux on impedance. Of them, 30 (76.9%) were women, mean BMI was 27.5+/-5.6, 12 (30.8%) were former smokers, and 3 (7.7%) had a history of narcotic or benzodiazepine use. On multivariate analysis, female gender (OR 6.29, p= 0.04) was the only factor that remained significantly associated with abnormal pharyngeal reflux, after controlling for potential confounders. Conclusion: Among patients with suspected LPR symptoms undergoing MII-pH with pharyngeal impedance channels, female gender was the only independent positive predictor for abnormal pharyngeal reflux events. Whether this represents a true increase in LPR prevalence among female patients, or different
Table 1. Demographics, MII-pH, and HREM parameters that may help distinguish LPR from CLD. Missing data in some patients may alter the N in the denominator, as specified in the table. MII-pH = multichannel intraluminal impedance and pH; HREM = high resolution esophageal manometry; LPR = laryngopharyngeal reflux; CLD = chronic lung disease; AET = acid exposure time; SD = standard deviation; NS = not significant.
S-243
AGA Abstracts
AGA Abstracts
EFFECT OF PROTON PUMP INHIBITION ON SURVIVAL IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: A META-ANALYSIS AND SYSTEMATIC REVIEW Sravanya Gavini, Wai-Kit Lo, Lawrence F. Borges, Alison Goldin, Walter W. Chan