| ObjectiveLarynghopharyngeal reflux (LPR) refers to the backflow of stomach contents above the upper esophageal sphincter, causing a set of symptoms and signs related to the pharynx and larynx. The reflux symptoms include hoarseness, sensations of something sticking in throat, clearing throat, chronic cough, dyspnea, dysphagia, and laryngospasm. It might lead to erythema and hyperemia in arytenoid, ventricular edema, vocal cold edema, vocal cord nodule, vocal cord polyp, disappearance of larynx ventricle, granuloma, false vocal cord, subglottic edema, and so on.Current diagnosis is lack of uniform standard. The Reflux Symptom Index (RSI) is self-administered and the Reflux Finding(RFS) Score depends on the experience of the laryngologist who grades it. Therefore, they are easily administered, but subjective. In this study, throat pain was the main symptom of some patients but RSI did not include. So diagnosis of LPR and measurement of the efficacy of PPI therapy could not only depend upon RSI and RFS which are subjective and not comprehensive.The current gold standard diagnostic test for LPR is dual-probe 24-hour pH monitoring, however, there are several limitations regarding the use of pH monitoring for LPR. The standard of PH value for the diagnosis of larynghopharyngeal reflux is controversial. The pH value decreased to<4.0 is regard as larynghopharyngeal reflux, but pepsin can damage the throat mucosa when the pH value is between 4.0 and 6.5, which leads to misdiagnosis in some patients.24-hour multichannel intraluminal impedance-pH monitoring could detect all kinds of reflux, including the weak acid reflux, nonacid reflux and gas reflux which the common pH monitoring could not detect.24-hour MII-pH monitoring is a objective and accurate technology which can quantitatively analyse reflux, recognizing the pH> 4 reflux which traditional pH monitoring can not identify and evaluating reflux events overall. It improves the specificity and sensitivity of LPR diagnosis and has certain directive significance to LPR treatment.Pepsin, as a major component of gastric juice, is an important pathogenic factor for larynghopharyngeal reflux. Pepsin is secreted only by gastric cells, so pepsin being discovered in the sputum or saliva is considered to be a pathological phenomenon. Pepsin being detected in any part outside the stomach means that reflux of gastric contents happens in the site. In our previous experiment, we have found detection of pepsin in sputum by immtmoassay could provide a high sensitive, noninvasive method for laryngopharyngeal reflux.The treatments for LPR currently are consisted of dietary and lifestyle modification along with proton pump inhibitor (PPI) therapy. Proton pump inhibitor (PPI) forms the cornerstone of antireflux therapy for LPR. It includes esomeprazole, omeprazole, rabeprazole, lansoprazole, and pantoprazole. Esomeprazole is the newest PPI, and reports have shown esomeprazole to provide better acid control than other PPI. However, published studies on the effect of PPI have so far yielded conflicting and often confusing results. Twice-daily dose PPI treatment for a minimum initial treatment for a period of 6 months in many patients with LPR is recommended.Vocal cord polyp is a common disease in'otorhinolaryngological department. Few studies have examined the relationship between LPR and vocal cord polyps. Recently, the role of LPR in the pathogenesis of laryngeal disorders has been emphasized. It may be related to loudly sound, long-term stimulation or chronic inflammation. It can also occur after a strong voice. In recent years, clinical studies have found that larynghopharyngeal reflux might lead to vocal cord nodules and vocal cord polyps. The relationship between vocal cord polyps and larynghopharyngeal reflux has gained attention. Acid without pepsin rarely causes mucosal damage. Squamous epithelium of vocal cord is more susceptible to acid and pepsin than any other parts of the throat.Based on the aboving background, this study will determine whether twice-daily PPI treatment for 8 weeks can demonstrat a significantly greater improvement in LPR symptoms and laryngeal appearance by measurement of levels of pepsin in sputum. Simultaneously, this study will evaluate the role of LPR as a risk factor in the vocal cord polyps by RSI scores, RFS scores, multichannel intraluminal impedance-pH monitoring, measurement of levels of pepsin in sputum, and examination of the expression of pepsin of all cases.Methods1. From June 2009 to Murch 2010, patients in the ENT outpatient department of Nanfang Hospital with symptoms of non-special chronic laryngopharyngitis were enrolled, having no significant improvement with regular treatment more than two months histories. Patients with a reflux symptom index (RSI)> 13 and a reflux finding score (RFS)> 7 were selected. Their sputum was obtained for pepsin assey. Twenty-six patients with positive resluts of pepsin assey were enrolled and received esomeprazole 20 mg twice daily for 8 weeks. They had return visits every two weeks. RSI scores, RFS scores and pepsin concentration in the sputum were assessed at baseline and after eight weeks. Pepsin in the sputum was measured by enzymelinked immunoadsorbent assay.2. From June 2010 to December2010, the tissue samples of vocal cord polyps were collected in the operation in the ENT department of Nanfang Hospital.31 cases of vocal cord polyp patients were assessed by RSI scores, RFS scores,24h multichannel intraluminal impedance-pH monitoring, and measurement of pepsin levels in sputum. The expression of pepsin was examined by immunothistochemical analysis in 31 laryngeal biopsy specimens of vocal cord polyps.3. Normal Q-Q (Quantile to Quantile) plots and P-P (Percentile to Percentile) plots were plotted for all RSI scores, RFS scores, pepsin concentration and ages. Shapiro-Wilk tests were also performed to obtain P values of the normality of the distribution. The Studentrs t-test, non-parametric test were used. The numeric data that were normally distributed are presented as Mean±sD. Numeric data not normally distributed are presented as median with 25% to 75% percentiles. Kappa values were calculated to compare pathologist assessment scores of two doctors. Kappa values greater than 0.70 showed a good degree of agreement; 0.40-0.70 showed the general degree of agreement; less than 0.40 indicated poor degree of agreement. Nonnormally distributed data for Spearman rank correlation. Spearman rank correlation was for assessing the association between pepsin concentration in sputum, expression of pepsin in vocal polyps, and results of MII-PH monitoring, A P value of less than 0.05 was taken as indicating statistical significance.The statistical analyses were done with SPSS computer software (version 13.0; SPSS). Results1.26 patients (11 women and 15 men; age range,18-60 years; mean,39.4 years) completed this study. All subjects in the study had moderate LPR with daily laryngopharyngeal symptoms and an average RSI scores of 20.9 points. After PPI treatment, patients had symptoms relief and the average RSI scores dropped to 10.8 points. Twenty-four of 26 patients (92.3%) had subjective improvements of their symptoms. The RSI reduction of all patients under PPI therapy was statistically significant (t=7.975,P=0.000).2. The average pre-treatment RFS scores was 9.9 [8.0; 11.1] and post-treatment was 6.3±2.1. The RFS reduction of all patients under PPI therapy was statistically significant (t=9.258,P=0.000).3. Pre-treatment average pepsin concentration was 11.4 [3.7; 17.2] ng/ml and the post-treatment concentration was 9.3[3.6; 13.9] ng/ml, and such difference was statistically significant. Twenty-one of 26 patients (80.8%) were reported on a dramatic decrease in pepsin sputum concentration. The pepsin concertration reduction of all patients under PPI therapy was statistically significant (Z=-3.213, P=0.001).4. RSI scores ranged from 3 to 31, with an average score 14.9±7.8. RSI scores of 15 vocal cord polyps patients (48.4%) were greater than 13. Scores of hoarseness or dysphonia, postnasal drip and clearing got higher scores.5. RFS scores ranged from 4 to 25, with an average score 12.0[11.0;15.0]. RFS scores of 29 vocal cord polyps patients (93.5%) were greater than 7.14 vocal cord polyp patients (45.2%) had RSI scores greater than 13 and RFS scores greater than 7.6. Pepsin concentration ranged from 0 to 23.7ng/ml, with an average score 10.4±6.0 ng/ml.2 patients had negative results while 29 had positive results.7. The results of 24h multichannel intraluminal impedance-pH monitoring: Demeester scores of 19 vocal polyp patients were more than 14.72, while scores of 12 patients less than 14.72, which meaned they had gastroesophageal reflux. In these 19 vocal polyp patients without gastroesophageal reflux,14 had nonacid reflux.8. Pepsin expression was in vocal polyp patients with strong positive results in 15 cases, positive results in 14 cases, weak positive results in 1 cases, and negative results in 1 cases.9. The correlations between pepsin concentration in sputum, expression of pepsin in vocal polyps, and results of MII-PH monitoring were compared. Significant difference was found between pepsin concentration in sputum and results of MII-PH monitoring (r=0.675, p=0.000). No significant difference was found between expression of pepsin in vocal cord polyps and results of MII-PH monitoring, as well as between expression of pepsin in vocal cord polyps and pepsin concentration in sputum (r=-0.086, p=0.647; r=0.128,p=0.494)Conclusions1. Twice-daily PPI treatment for 8 weeks with lifestyle modifications could significantly improve symptoms and laryngeal appearance for most LPR patients with decreased levels of pepsin in sputum.2. There was a correlation between LPR and vocal cord polyps. The results of 24h multichannel intraluminal impedance-pH monitoring:Demeester scores of 19 vocal cord polyp patients were more than 14.72, while scores of 12 patients less than 14.72, which meaned they had gastroesophageal reflux. In these 19 vocal polyps patients without gastroesophageal reflux,14 had nonacid reflux.3. Pepsin expression was in vocal cord polyp patients with strong positive results in 15 cases, positive results in 14 cases. LPR was present in patients with vocal cord polyps, it seemed to be the causative factor of vocal cord polyps; pepsin could contribute to the development of vocal cord polyps. |
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