Andrea Nacci

How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?

AIM To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR). METHODS Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE). RESULTS The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m(2). All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively). CONCLUSION MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.

Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo: Effectiveness of Two Different Methods of Treatment

The aim of this study is to compare the results obtained using 2 methods of treatment for horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV): the barbecue maneuver + forced prolonged position (FPP) versus the Gufoni maneuver. In a randomized prospective clinical trial, we recruited 147 patients affected by HSC-BPPV. The primary outcome was the absence of vertigo and nystagmus upon application of the supine roll test during the follow-up examination. A statistical evaluation was performed in order to assess whether any parameters (e.g. age, duration of nystagmus and symptoms) could influence in any way the results obtained with the 2 methods of treatment. One hundred and three of the 147 patients affected by HSC-BPPV had the geotropic form and 44 had the apogeotropic type. We were able to transform 29 cases of HSC-BPPV from apogeotropic to geotropic. Finally, we obtained a group of 112 patients who were randomized either to the barbecue + FPP procedure (54 patients) or to the Gufoni maneuver (58 patients). The most evident result is the higher percentage of success (statistically significant) with the Gufoni maneuver at the first session of treatment (86 vs. 61%). The final control showed that 44 out of 54 (81%) patients treated with the barbecue maneuver + FPP were symptom free compared to 54 out of 58 (93%) treated with the Gufoni maneuver. Both the barbecue maneuver + FPP and the Gufoni maneuver are valid methods for treating HSC-BPPV (geotropic forms). However, our results also indicate that the Gufoni maneuver has a significant advantage: the success rate shown at the follow-up, although without statistical significance, is undoubtedly higher (93 vs. 81%). This result, together with the fact that it is very easy to perform and that patient compliance is better, make the Gufoni maneuver the method of choice in HSC-BPPV treatment.

Transtympanic Steroids as a Salvage Therapy in Sudden Hearing Loss: Preliminary Results

Purpose: To understand the real efficacy of transtympanic steroid therapy for sudden sensorineural hearing loss (SSHL) in patients in whom traditional therapies have failed. Procedures: A prospective study was designed in order to evaluate hearing improvement in SSHL patients treated with transtympanic therapy. A solution of methyl-prednisolone (MP) and sodium bicarbonate was administered via a transtympanic injection to 8 patients. Hearing level was evaluated before therapy and at days 1, 7 and 30. Results: Hearing improvement was obtained in 75% of the patients. The patients in this category are usually considered untreatable. Conclusion: Transtympanic steroid therapy is an efficacious solution for patients affected by SSHL in whom traditional therapies have failed. Further studies will be required to identify the most favourable dosage, route of administration and type of steroid. Transtympanic steroid application is safe, inexpensive, easy to perform and efficacious in cases of SSHL not responsive to traditional therapy.

Assessment of Swallowing by Oropharyngoesophageal Scintigraphy in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in adults, and dysphagia is one of its most frequent and disabling symptoms. Oropharyngoesophageal scintigraphy (OPES) permits a functional and semiquantitative study of the various stages of swallowing. We studied 28 ALS patients (12 females and 16 males; mean age = 63.57 ± 10.39 yr SD), who were clinically rated against the ALSFRS scale (Amyotrophic Lateral Sclerosis Functioning Rating Scale) and underwent OPES with 99mTc-nanocolloid using either a liquid or a semisolid bolus. The semiquantitative parameters we analyzed were Oral Transit Time (OTT), Pharyngeal Transit Time (PTT), Esophageal Transit Time (ETT), Retention Index (RI), and Esophageal Emptying Rate (EER10s). Hence, the OPES performed with a semisolid bolus produced a higher proportion of pathologic values for the swallowing variables than when liquid bolus was used. Analyzed by grouping the patients into classes according to their bulbar ALSFRS scores, we found a significant increase in the OTT (p < 0.005), PTT (p < 0.02), and Oropharyngeal Retention Index (OPRI) (p < 0.0004) variables in ALS patients with more severe bulbar involvement. OPES has turned out to be a very important examination for detecting tracheal-bronchial inhalation and it also offers the possibility of acquiring a semiquantitative evaluation of the amount of food inhaled. In our experience, OPES in patients with ALS has been easy to use, economic, well tolerated, and capable of supplying precise indications with regard to the extent of the swallowing disorder, which permits a better clinical definition of the ALS patient.

Antibodies to inner ear antigens in Meniere's disease

Menieres disease (MD) is an idiopathic inner ear disorder characterized by fluctuating hearing loss, episodic vertigo and tinnitus. Its aetiology is unknown, although there is growing evidence that autoimmunity may be involved in its development. Using the Western blot immunoassay, we examined the reactivity to bovine inner ear antigens of sera from a series of MD patients who had previously been extensively studied for the presence of antibodies to collagens and membrane proteins. Reactivity to inner ear antigens of molecular weight 44 and 53 kD was found in 11/25 (44%) and 10/25 (40%) of the patients, respectively; both antigens were absent in the sera of healthy donors. It is still unclear whether the antibodies to 44 and 53 kD proteins play a role in the pathogenesis of MD or if they instead represent the result of inflammation and tissue destruction. Even if the latter is true, they may contribute to the perpetuation of the disease or play a role as a cofactor in association with other mechanisms.

Optimal treatment of laryngopharyngeal reflux disease

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies.

Possible association between thyroid autoimmunity and Menière's disease

Various aetiopathological mechanisms have been postulated to be at the root of Menières disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non‐selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear–vestibular function and analysis of thyroid‐stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti‐TSH receptor antibody (TR‐Ab), anti‐thyroperoxidase antibody (TPO‐Ab) and anti‐thyroglobulin antibody (Tg‐Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66·7% TPO‐Ab and 33·3% Tg‐Ab] was superimposable with the healthy controls [6/82 (7%); 66·7% TPO‐Ab and 33·3% Tg‐Ab]. In contrast, 38% of the MD patients (P = 0·0001 versus group A and group B) had significant autoantibody levels (68·4% TPO‐Ab; 15·8% TPO‐Ab + TR‐Ab; 10·5% Tg‐Ab; 5·2% TPO‐Ab + Tg‐Ab). Furthermore, 14% of the MD patients were hyperthyroid under l‐thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi‐disciplinary clinical investigation.

Sex Hormone Receptors in Vocal Fold Tissue: A Theory about the Influence of Sex Hormones in the Larynx

Objective: The larynx is considered a secondary sexual organ. To demonstrate that sex hormones can directly influence laryngeal function, specific receptors in the vocal cord must be identified. Materials and Methods: We searched for estrogen, progesterone and androgen receptors, using an immunohistochemical method, in normal human vocal cords (from 3 cadavers) and in samples of healthy vocal cords and of laryngeal carcinomas from 15 live subjects. Breast and prostate carcinoma were used as controls. Results: In all the normal samples tested, the results were negative; there was only a nonspecific cytoplasmatic response in the subepithelial glands (false positives). In the neoplastic tissue, 2 samples had a weak nuclear focal positivity for estrogen and progesterone receptors; all 15 subjects studied were negative for androgen receptors. Conclusions: Since our data show that sex hormone receptors are absent in the vocal cords, other theories must be considered to explain the fact that hormones influence the quality of the voice. This study discusses the possibility that the changes of voice according to gender and throughout life might be linked with a different expression of some growth factors in the laryngeal tissue and that this expression might in turn be influenced by hormonal variations.

Elevated Antithyroid Peroxidase and Antinuclear Autoantibody Titers in Ménière’s Disease Patients: More than a Chance Association?

Objective/Hypothesis: The aim of this prospective study is to evaluate the possible association between Ménière’s disease (MD) and autoantibodies. Methods: Fifty-five patients with definite MD (51 unilateral and 4 bilateral) were matched with 55 patients with unilateral vestibular paresis without cochlear involvement and 55 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, anti-TSH receptor antibody, antithyroperoxidase antibody, antithyroglobulin antibody and of antibodies to non-organ-specific antigens, namely antinuclear antibodies, antibodies to extractable nuclear antigens and antineutrophilic cytoplasmic antibodies. Results: Thirty-three subjects (60%) of the MD group had 1 or more elevated serum autoantibody levels, both organ and non-organ specific; 16 patients (29.1%) with unilateral vestibular paresis had 1 or more elevated serum autoantibody levels, while 13 healthy subjects (23.6%) had 1 or more elevated serum autoantibody levels. Conclusions: Based on our data we speculate that there is a more than a chance association between MD and ‘autoimmunity’, thus suggesting a hypothetical role of the immune system in MD pathogenesis. In other words, a pathogenetic role of an ‘immune dysregulation’ in MD patients can be hypothesized.

Plasma Homocysteine, Folate, and Vitamin B12 Levels in Patients With Laryngeal Cancer

OBJECTIVE To determine plasma levels of homocysteine, folate, and vitamin B12 in patients with laryngeal cancer and a control group. DESIGN Analysis of homocysteine, folate, and vitamin B12 levels in 25 consecutive untreated patients with laryngeal carcinoma and 80 healthy control participants. The study and control groups were subdivided into smokers, ex-smokers, and nonsmokers, as well as drinkers and nondrinkers. INTERVENTION The AxSYM system was used to measure total homocysteine levels, and the ARCHITECT system (both Abbott-Diagnostics Division) was used to measure folate and vitamin B12 levels. MAIN OUTCOME MEASURES Homocysteine, folate, and vitamin B12 levels. RESULTS The mean (SD) level of total homocysteine in patients with laryngeal carcinoma was 2.84 (1.62) mg/L vs 0.99 (0.24) mg/L in the control group (P <.001). The mean (SD) folate plasma level was 4.3 (2.2) ng/mL vs 7.9 (2.4) ng/mL (P <.001). CONCLUSIONS Metabolic alterations in homocysteine, folate, and vitamin B12 levels, especially hypofolatemia, could be associated with laryngeal cancer. Lengthier follow-up studies and larger groups of patients will help determine the real role of these metabolic alterations.