Relationship between time of exposure of laryngopharyngeal reflux and gene expression in laryngeal fibroblasts.

OBJECTIVES: Acid reflux is damaging to the laryngeal mucosa; however, the significance of the duration of reflux episodes has not been evaluated. The purpose of this study was to determine whether varying the exposure times at low pH with or without pepsin alters gene expression in laryngeal fibroblasts. METHODS: Human false vocal fold and postcricoidal cultures were exposed to pH 4 or pH 5 media with and without pepsin for 10, 30, 60, and 240 seconds. Using a real-time polymerase chain reaction, we determined the messenger RNA expression of TGFbeta-1, VEGF, FGF-2, EGR-1, ATF-3, CTGF, MMP-1, MMP-2, and decorin. RESULTS: Molecular responses were initiated at pH 5. Postcricoidal fibroblasts were more sensitive than false vocal fold fibroblasts to the presence of pepsin. Changes in transcript levels were dependent on acid exposure time, and the most significant changes were measured during the first 60 seconds after exposure. CONCLUSIONS: Time of exposure to acid and pepsin needs to be taken into consideration when determining limit of pathology in pharyngeal reflux. Genes are identified that are induced by low pH and that may be of potential importance in the pathogenesis of reflux laryngitis.

Helicobacter pylori infection and its correlation to extraesophageal and esophageal reflux in contact granuloma patients.

To evaluate the presence of Helicobacter pylori (H. pylori) infection and its correlation to extraesophageal and esophageal reflux, 18 consecutive contact granuloma patients were examined by laryngoscopy, 24-hour double probe pH monitoring and [13C]-urea breath test. Sixteen of the 18 patients (89%) were H. pylori-negative, while 2 patients (11%) showed positive test results. Extraesophageal reflux was detected in 14 patients; one of them was H. pylori-positive. In the ten patients with abnormal distal esophageal reflux, one was H. pylori-positive. The present results do not confirm increased prevalence for H. pylori infection in contact granuloma patients and the occurrence of H. pylori infection was not correlated to the amount of pharyngeal or esophageal acid exposure.

Screening and rehabilitation of olfaction after total laryngectomy in Swedish patients: results from an intervention study using the Nasal Airflow-Inducing Maneuver.

OBJECTIVES: To examine the olfactory function in patients with laryngectomy and to assess the results of the Nasal Airflow-Inducing Maneuver (NAIM) odor-rehabilitation technique. DESIGN: A prospective intervention study. SETTING: University hospital. PATIENTS: Twenty-four patients, 21 men and 3 women, mean age 68 years, who underwent laryngectomy at least 5 months prior to intervention. INTERVENTION: Speech therapists trained patients in the NAIM technique: simultaneous lowering of the jaw, floor of the mouth, tongue, base of the tongue, and soft palate while the lips are closed. Three interventions were given within 6 weeks. MAIN OUTCOME MEASURE: Olfactory testing with semistructured interview, the Questionnaire on Olfaction, Taste, and Appetite (QOTA), and the Scandinavian Odor-Identification Test (SOIT). Quality of life was measured with European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. The patients were categorized as smellers or nonsmellers based on the SOIT results. RESULTS: Before the treatment, 10 patients (42%) were smellers (ie, 6 had normosmia and 4 hyposmia), while 14 patients (58%) were nonsmellers (ie, all had anosmia). Thus, 18 patients had impaired olfaction. Using the NAIM technique, 13 (72%) of 18 patients with impaired olfaction showed improvement. Of the 14 nonsmellers, 7 converted to smellers after only 1 intervention session, giving us a success rate of 50% in anosmic patients after 1 session. CONCLUSIONS: Olfactory impairment is common in patients who underwent laryngectomy. The NAIM method is easy to learn and rapidly improves smell and taste. A single intervention session is sometimes sufficient, but many patients benefit from repeated training. The SOIT test is an effective and simple test for the assessment of olfaction acuity after laryngectomy.

Pharyngeal reflux episodes at pH 5 in healthy volunteers.

OBJECTIVE: The clinically used cut-off limit in reflux disease is pH 4. Yet, earlier studies have shown a poor correlation between pharyngeal reflux episodes and symptoms or laryngeal findings, and treatment results have been suboptimal. Moreover, recent data suggest that pepsin is still active at pH 5. The aim of this study was to evaluate the occurrence of pharyngeal pH 5 reflux episodes in healthy controls and to correlate these to the pH monitoring results with a cut-off limit of pH 4. MATERIAL AND METHODS: The results of double-probe 24-h pH monitoring from 35 healthy controls were reanalysed concerning the occurrence of pH decreases to pH 5. RESULTS: Pharyngeal pH 5 reflux episodes occurred in 32 healthy controls (91%). The median number of pharyngeal reflux episodes at pH 5 was 4.0. The vast majority of these reflux episodes (92%) occurred in the upright position, especially in the postprandial period. The median time pH < 5 in the pharynx was 0.1% while the upper limit of normality was 1.5%. Pharyngeal pH 5 reflux episodes were 5 times more common than pH 4 reflux episodes. There was a significant positive correlation between hypopharyngeal and oesophageal acid exposure time at both pH 4 and 5 (p<0.01). CONCLUSIONS: Pharyngeal pH 5 reflux episodes are present in most healthy adults, mainly in upright position and in the postprandial period. The importance of these episodes for the occurrence of laryngeal symptoms and signs and for treatment response needs to be prospectively assessed.

Effect of acid and pepsin on gene expression in laryngeal fibroblasts.

The aim of this study was to determine changes that momentary low pH with or without pepsin causes in gene expression in laryngeal fibroblasts. Cell cultures were established from human false vocal fold (FVF) and postcricoidal (PC) mucosae. Using a real-time polymerase chain reaction, we analyzed messenger RNA gene expression of growth factors (transforming growth factor beta1, vascular endothelial growth factor, fibroblast growth factor 2), matrix metalloproteinases (MMP-1, MMP-2), and decorin in normal media, pH 4 media, and pH 5 media with and without pepsin. The FVF fibroblast gene expression differed substantially from the PC fibroblast gene expression. No significant interaction effects for acid and pepsin were found in the FVF culture, but in PC cultures we found a significant overexpression interaction effect for vascular endothelial growth factor, fibroblast growth factor 2, MMP-1, MMP-2, and decorin. These results imply that PC tissue is more sensitive than FVF tissue to the noxious effects of gastric contents. Furthermore, there appears to be a synergistic effect for acid and pepsin exposure in the posterior larynx.

Prevalence of extraesophageal reflux in patients with symptoms of gastroesophageal reflux.

OBJECTIVES: To compare the prevalence of extraesophageal reflux (EER) in patients with heartburn, posterior laryngitis (PL), and in healthy controls. Study design and setting A retrospective and prospective study including a total of 101 subjects who underwent 24-hour dual-probe pH monitoring. RESULTS: 52% of the subjects with heartburn had EER. No significant differences were found between the PL and heartburn groups for any pharyngeal reflux parameters. However, supine pharyngeal reflux was significantly more prevalent in heartburn patients with GERD than in PL patients and healthy controls (P < 0.05). Significant positive correlation (P < 0.01) was found between the percentage of time pH <4 in the pharynx and in the distal esophagus. CONCLUSION: EER occurs in the majority of heartburn patients who are lacking laryngeal symptoms. Abnormal distal esophageal acid exposure makes the occurrence of EER more likely. SIGNIFICANCE: EER appears to be a continuum without clear-cut differences between the groups.

Extraesophageal reflux in patients with contact granuloma: a prospective controlled study.

The aim of this study was to compare the incidences of extraesophageal reflux in patients with contact granuloma and healthy controls. A 24-hour ambulatory pH monitoring technique was used to measure reflux parameters in the pharynx and distal esophagus. Pharyngeal acid reflux events occurred in 17 of 26 granuloma patients (1 to 20 episodes per patient) and 5 of 19 controls (1 to 8 episodes per subject). The reflux episodes were typically short and occurred predominantly in an upright position. A comparison between the groups showed a significant difference in the number of pharyngeal reflux episodes (p = .009) and in the total time of pH below 4 (p = .006). On the other hand, we found no significant differences in any esophageal reflux parameters, except for the percentage of distal esophageal reflux episodes that reached the pharynx (p = .006). In this study, pharyngeal acid exposure was significantly more prevalent in patients with contact granuloma than in healthy controls.

Gastroesophagopharyngeal reflux in patients with contact granuloma: a prospective controlled study.

The aim of this study was to compare the incidences of gastroesophagopharyngeal reflux in patients with contact granuloma and healthy controls. A 24-hour ambulatory esophagopharyngeal pH monitoring technique was used to measure reflux parameters in the pharynx and distal esophagus. Pharyngeal acid reflux events occurred in 17 of 26 granuloma patients (1 to 20 episodes per patient) and 5 of 19 controls (1 to 8 episodes per patient). The reflux episodes were typically short and occurred predominantly in an upright position. A comparison between the groups showed a significant difference in the number of pharyngeal reflux episodes (p = .009) and in the total time of pH below 4 (p = .006). On the other hand, we found no significant differences in any esophageal reflux parameters, except for the percentage of distal esophageal reflux episodes that reached the pharynx (p = .006). In this study, pharyngeal acid exposure was significantly more prevalent in patients with contact granuloma than in healthy controls.