Introduction

Patients presenting with laryngeal complaints are often considered to harbor atypical esophageal laryngo-pharyngeal reflux (LPR). The association between LPR symptoms and gastroesophageal reflux (GER) is an ongoing debate.

Aims & Methods

We aimed to characterize patients referred for investigation of LPR complaints and to compare them to patients referred with classic reflux complaints.

All patients referred for pH-impedance testing were offered to participate in this cross-sectional observational study. Those included underwent a comprehensive workup including medical history (presence of a neurologic disease, diabetes, foregut surgery, depression, a diagnosis of Irritable bowel syndrome (IBS) or peptic disease), filling a symptom questionnaire, Rome 3, SCL 90 and SF 36 questionnaires. IBS, functional dyspepsia (FD) and other conditions were defined according to Rome 3 criteria.
All patients underwent gastroscopy, esophageal HRM (Chicago 3) and pH-impedance testing off therapy.
Classic reflux complaints were defined as heartburn, regurgitation, and chest pain. Atypical reflux/LPR symptoms included cough, hoarseness, throat clearing, globus sensation, and asthma exacerbation.
Of patients with symptoms during the study (104/156=(67%), functional heartburn was diagnosed in 33% vs.50.0%, p=0.094.

Results

156 patients were included, 53% were females and with mean age of 53±17y. The indication for testing was classic reflux in 90 (58%), and 66 (42%) patients were referred for LPR symptoms. No significant differences were found between the groups in demographic parameters, background diseases and psychological profile. Both classic and LPR groups had a high prevalence of Rome 3-IBS (67% and 59%, p-NS) and FD (56% and 32%, p=0.058), respectively.
Patients with classic reflux symptoms, compared to the LPR group, used more PPI`s (90% vs. 73%, p=0.008) and SSRI`s (19% vs. 8%, p=0.053) respectively. Life quality was not different between the groups. Gastroscopy and HRM diagnoses and LES and esophageal body parameters were similar between the 2 groups. A higher upper esophageal sphincter pressure was noted in the classic reflux group (p=0.011). Esophageal acid exposure time (AET) was similar as well in the classic vs. the LPR group: 5% vs.5.4%, p=NS, as was the number of patients with AET>6%: 36% vs. 35%, p=NS, respectively. The median number of weakly acidic reflux and non-acidic episodes was also similar: 27 vs. 24, p=NS and 2 (0-2) vs. 1 (0-2), p=NS, respectively.
Of patients with symptoms during the study (104/156=(67%), functional heartburn was diagnosed in 33% vs.50.0%, p=0.094.

Conclusion

In our cohort, the majority of patients with LPR had normal esophageal acid exposure, while the prevalence of IBS, functional dyspepsia, and functional heartburn was higher than reported world prevalence. While other mechanistic explanations may exist, our study suggests an overdiagnosis of LPR symptoms to be related to acid gastro esophageal reflux.

Introduction

Fatigue, defined as “an overwhelming sense of tiredness, lack of energy and feeling of exhaustion” [1] is a frequent complaint in celiac disease. A strict, lifelong gluten free diet is the only established treatment for celiac disease, however its long-term effect on fatigue is unknown.

Aims & Methods

Our aims were to investigate the course of fatigue severity and prevalence in celiac patients from diagnosis to five to seven years on a gluten free diet, and to investigate whether diet adherence, disease activity and selected biochemical markers are associated with fatigue.
We conducted a single-center prospective study in 45 patients with newly diagnosed celiac disease. The primary endpoints were fatigue severity, as measured by the Fatigue Severity Scale (FSS) [2], the fatigue Visual Analog Scale (fVAS) [3], and the Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs) [4]. SF-36vs scores were inverted (100 – SF-36vs = inverted SF-36vs) to ease comparison between the other scales, so that higher scores indicate more fatigue. Clinically relevant fatigue was defined by an FSS score of ≥4, a fVAS score of ≥50, and an inverted SF-36vs score of ≥65. Study visits were performed at the time of diagnosis (Visit 1), after adhering to a gluten free diet for one year (Visit 2) and for five to seven years (Visit 3). Diet adherence was evaluated through urinary gluten immunogenic peptides (GIP) and the Celiac Diet Adherence test (CDAT) [5]. Disease activity was assessed through Celiac Symptom Index (CSI) [6], celiac autoantibodies (anti tissue transglutaminase IgA and deamidated gliadin peptide IgG) and histologic evaluation (Marsh score). Nutritional status was assessed through BMI, hemoglobin, 25-hydroxy vitamin D, cobalamin, ferritin and folic acid levels.

Results

Fatigue severity was significantly reduced from time of diagnosis, for all three instruments (Table 1). Fatigue prevalence rates were significantly decreased from Visit 1 (40-53%) to Visit 3 (27-31%). Fatigue was significantly lower in patients with good adherence compared to patients with poor adherence according to CDAT scores (For FSS p=0.022, fVAS p=0.017, and for inverted SF-36vs p=0.033). There was however no difference in fatigue severity between adherent and nonadherent patients when evaluating adherence through urinary GIP. Fatigue was lower in patients in clinical remission according to CSI scores (for FSS p=0.002, fVAS p=0.004, and for inverted SF-36vs p=0.002), but not associated with autoantibodies or nutritional status. In multiple linear regression analysis, depression was the only independent variable significantly associated with all three fatigue measures at Visit 3, whereas pain was positively associated with inverted SF-36vs scores.

Table 1.

Conclusion

Fatigue remains a frequent complaint in celiac disease even after five to seven years on a gluten free diet. However, fatigue severity is reduced from time of diagnosis. Fatigue was associated with dietary adherence as assessed by CDAT. Disease activity according to CSI was associated with fatigue, whereas nutritional status, autoantibodies and histologic changes were not.

References

1. Krupp, L.B. and D.A. Pollina, Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol, 1996. 9(6): p. 456-60.
2. Krupp, L.B., et al., The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol, 1989. 46(10): p. 1121-3.
3. Wolfe, F., Michaud K, Pincus T, Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis. J Rheumatol, 2005. 32(7): p. 1261-6.
4. Ware, J.E., Jr. and C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83.
5. Leffler, D.A., et al., A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(5): p. 530-6, 536.e1-2.
6. Leffler, D.A., et al., A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(12): p. 1328-34, 1334.e1-3.

Disclosure

Berit Mære Skjellerudsveen: Received lecture honoraria from Takeda for lectures on IBD and pregnancy. This study is partly funded by a grant from the patient organization “The Norwegian Coeliac Society”.

Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Laryngopharyngeal Reflux (LPR) is a common troublesome complaint in clinical practice. The treatment outcomes were unsatisfied given unclear pathophysiology and lack of gold standard test. Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) had been used to help with the diagnosis while esophageal multichannel intraluminal impedance (MII)/pH monitoring is the most reliable tool to evaluate gastroesophageal reflux disease (GERD). The role of MII/pH monitoring in extra-esophageal GERD is controversial.

Aims & Methods

We aimed to evaluate the benefit of MII/pH monitoring results in patients with LPR defined by clinical scoring of RSI ≥ 13 points and/or RFS ≥ 7 points.
Patients with definite LPR diagnosed by otolaryngologists using predefined RSI and RFS were recruited. All participants underwent esophageal manometry and off-PPI MII/pH monitoring. The results of MII/pH findings and clinical scores were determined for the correlation.

Results

A total of 100 (71 Female, 29 Men) LPR patients were enrolled, with the mean age of 50.1 years. The mean RSI and RSF score were 18.4±6.1 and 9.8±4.1 respectively. Half of the patients had abnormal manometry; 48% had ineffective esophageal motility (IEM) and 9% had low lower esophageal sphincter pressure (LESP). The median acid exposure time (AET) was 1.85% and the median number of reflux episodes and proximal reflux episodes were 29.5 and 4 respectively.Gas reflux is the most common type of reflux with 98% of population. There was a significant correlation between RSI and the number of gas reflux (r = 0.255, P-value 0.011). There was no difference in RSI and RFS in all MII/pH parameter subgroups, including pathological vs non-pathological acid reflux, a high vs low DeMeester score, a high vs low number of reflux, proximal reflux, or acid reflux.

Correlation between RSI or RFS and MII/pH finding

Conclusion

In this population, there were no significant acid refluxes in patients with LPR diagnosed by standard cut-off score of RSI and/or RFS. However, RSI had significant correlation with gas reflux episodes. Interestingly, up to 60% of the participants had IEM or low LESP. These findings are still be scrutinized.

References

1. Vaezi, M.F., et al., Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol, 2003. 1(5): p. 333-44.
2. Belafsky, P.C., G.N. Postma, and J.A. Koufman, Validity and reliability of the reflux symptom index (RSI). J Voice, 2002. 16(2): p. 274-7.
3. Belafsky, P.C., G.N. Postma, and J.A. Koufman, The validity and reliability of the reflux finding score (RFS). Laryngoscope, 2001. 111(8): p. 1313-7.
4. Ahmed, T. and M.F. Vaezi, The role of pH monitoring in extraesophageal gastroesophageal reflux disease.Gastrointest Endosc Clin N Am, 2005. 15(2): p. 319-31.
5. Joniau, S., et al., Reflux and laryngitis: a systematic review. Otolaryngol Head Neck Surg, 2007. 136(5): p. 686-92.
6. Chang, B.A., et al., The Reliability of the Reflux Finding Score Among General Otolaryngologists. J Voice, 2015. 29(5): p. 572-7.

Introduction

Celiac disease (CD) is a complex multi-systemic autoimmune disease. The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after GFD. There is still little evidence on the best method for assessing gluten-free diet (GFD) adherence and mucosal recovery during treatment.

Aims & Methods

The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016-2021.We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis.

Results

A total of 102 patients were enrolled, two thirds were females, median age of 39 yrs. The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while 23(22.5%) cases showed mild enteropathy (Marsh 1,2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). The multivariate Cox regression analysis demonstrated that complete mucosal atrophy (p = 0.007) and high AGA antibody levels (p = 0.001) were independent risk factors for a lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR.

Conclusion

Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Disclosure

nothing to disclose