Efficacy of inhaled budesonide on serum inflammatory factors and quality of life among children with acute infectious laryngitis.

OBJECTIVE: Acute infectious laryngitis is commonly occurred among children. Our study sought to investigate the effect of inhaled budesonide on among children with acute infectious laryngitis. METHODS: A total of 92 children with acute infectious laryngitis were randomly allocated to either the study (46 cases, treated with inhaled budesonide) and control group (46 cases, treated with dexamethasone). The disappearance time of symptoms, therapeutic effect and adverse reactions were observed in the two groups. RESULTS: The therapeutic effect was significantly better in the study group than in the control group (97.83% vs 82.61%). After 3 days of treatment, the disappearance time of symptoms, such as hoarseness/barking cough, singing sound in the throat, three-concave sign and dyspnea in the study group was significantly less than that in the control group (P < 0.05). The levels of IL-4, IL-17, MMP-9, IL-33, IFN-γ and IgE in the two groups decreased, and evidently lower levels were found in the study group as compared to the control group (P < 0.05). CONCLUSION: Inhaled budesonide exerted obvious better effect in terms of reducing serum inflammatory factors and improving the quality of life with safety profile.

Association of mRNA Expression Levels of LRP1 and Actin-Binding Proteins with the Development of Laryngeal and Laryngopharyngeal Squamous Cell Carcinoma.

We analyzed the association of the level of mRNA expression of the main endocytosis receptor LRP1 and actin-binding proteins (ezrin, profilin-1, cofilin-1, and adenylyl cyclase-associated protein 1) with the development and metastasis of laryngeal and laryngopharyngeal squamous cell carcinoma. The mRNA expression was evaluated in paired tissue samples using quantitative reverse transcription real-time PCR (RT-qPCR) and SYBR Green reagents. The study included 38 patients with stage T1-4N0-1M0 laryngeal and laryngopharyngeal squamous cell carcinoma and 10 patients with chronic hyperplastic laryngitis or grade II-III epithelial dysplasia. The expression of LRP1 in patients with laryngeal and laryngopharyngeal squamous cell carcinoma depended on the stage of the tumor process. Against the background of low expression of LRP1 mRNA, the relationship between cofilin 1 and profilin 1 expression became stronger (r=0.08; p=0.05) and a correlation between cofilin 1 and esrin expression (r=0.7; p=0.05) appeared. Studies on a larger patient cohort are required to make a definite conclusion on the role of LRP1 in the development of laryngeal and laryngopharyngeal squamous cell carcinoma.

The Acute Phase Proteins Reaction in Children Suffering from Pseudocroup.

The aim of the study was to evaluate the inflammatory reaction in children with pseudocroup and compare it with other laryngological diseases according to the available literature data. The study group included 51 children hospitalized because of pseudocroup. The measurements of the acute phase proteins (APP), such as C-reactive protein (CRP), alpha-1-antitrypsin (AT), alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein (AGP), ceruloplasmin (Cp), transferrin (Tf), alpha-2-macroglobulin (A2M), and haptoglobin (Hp) were obtained at 3 time points. The glycosylation profiles of AGP, ACT, and Tf were completed. An increased AGP level was observed in girls. The AGP glycosylation revealed the advantage of the W0 variant over the W1 variant. W1 and W2 were decreased in boys. W3 emerged in boys. The Tf concentration and T4 variant were lower compared to the control group. The A2M level was lower after treatment. The Hp and AT levels were decreased a few weeks later. The ACT glycosylation revealed a decrease of the A4 variant in boys. In conclusion, the inflammatory reaction during pseudocroup was of low intensity. The APP glycosylation suggested a chronic process. In a follow-up investigation, no normalization of the parameters was noted, but signs of persistent inflammation were observed.

Laryngeal mucus hypersecretion is exacerbated after smoking cessation and ameliorated by glucocorticoid administration.

INTRODUCTION: The mechanisms underlying the effects of cigarette smoke and smoking cessation on respiratory secretion, especially in the larynx, remain unclear. OBJECTIVES: The aims of this study were to determine the effects of cigarette smoke and smoking cessation on laryngeal mucus secretion and inflammation, and to investigate the effects of glucocorticoid administration. METHODS: We administered cigarette smoke solution (CSS) to eight-week-old male Sprague Dawley rats for four weeks, then examined laryngeal mucus secretion and inflammatory cytokine expression on days 1, 28 and 90 after smoking cessation. We also investigated the effects of the glucocorticoid triamcinolone acetonide when administered on day 1 after smoking cessation. RESULTS: Exposure to CSS resulted in an increase in laryngeal mucus secretion that was further excacerbated following smoking cessation. This change coincided with an increase in the expression of mRNA for the inflammatory cytokines tumor necrosis factor and interleukin-6, as well as mRNA for MUC5AC, which is involved in mucin production. Triamcinolone suppressed CSS-induced laryngeal mucus hypersecretion and pro-inflammatory cytokine production. CONCLUSION: Cigarette smoke-associated inflammation may contribute to the exacerbated laryngeal mucus hypersecretion that occurs following smoking cessation. The inflammatory response represents a promising target for the treatment of cigarette smoke-associated mucus hypersecretion.

Effects of Smoke Generated by Electrocautery on the Larynx.

OBJECTIVE: The aim of this study was to investigate effects of smoke produced by electrocautery on the laryngeal mucosa. MATERIALS AND METHODS: We used 16 healthy, adult female Wistar albino rats. We divided the rats into two groups. Eight rats were exposed to smoke for 60 min/d for 4 weeks, and eight rats were not exposed to smoke and served as controls. The experimental group was maintained in a plexiglass cabin during exposure to smoke. At the end of 4 weeks, rats were sacrificed under high-dose ketamine anesthesia. Each vocal fold was removed. An expert pathologist blinded to the experimental group evaluated the tissues for the following: epithelial distribution, inflammation, hyperplasia, and metaplasia. Mucosal cellular activities were assessed by immunohistochemical staining for Ki67. Results taken before and after effect were compared statistically. RESULTS: There was a significant difference in the extent of inflammation between the experimental group and the control group. Squamous metaplasia was detected in each group, but the difference was not significant. None of the larynges in either group developed hyperplasia. CONCLUSIONS: We showed increased tissue inflammation due to irritation by the smoke.

[The influence of endogenous intoxication on the clinical picture of various forms of acute stenosinglaryngotracheitis in the children].

The objective of the present study was to evaluate the influence of endogenous intoxication on the clinical picture of various forms of acute stenosinglaryngotracheitis in the children. The clinical and laboratory examination involved 275 patients presenting with this pathology. Special emphasis was laid on diagnostics of the character and severity of intoxication syndrome. To this effect, we carried out a dynamic study of variations in the blood levels of medium molecular weight peptides, the toxic blood factor, and circulating immune complexes (CIC). It is concluded that the parameters of endogenous intoxication in the children with acute stenosinglaryngotracheitis are directly related to the specific clinical features and severity of this disease.

Expression of claudin-3 in the esophagus and larynx of rat reflux model.

OBJECTIVE: The aim of this study was to investigate the association between laryngeal expression of claudin-3 and laryngopharyngeal reflux (LPR) in a rat reflux model. METHODS: Eight Wistar rats were divided into two groups. Four rats underwent total esophageal myectomy to induce reflux, and the remainder underwent a sham operation as a control. All animals were sacrificed 12 weeks after surgery to perform tissue histology and Western blot analysis. RESULTS: Lymphocyte infiltration increased significantly in the study group in both esophageal and laryngeal samples (P=0.001, 0.002, respectively). Both esophageal and laryngeal expressions of claudin-3 were significantly lower in the study group when compared with that in the control group (P=0.045, 0.037, respectively). CONCLUSION: The results of this study suggest that a decrease in claudin-3 could be a sensitive indicator of reflux laryngitis in rats.

Role of steroids in acute phonotrauma: A basic science investigation.

OBJECTIVES/HYPOTHESIS: Steroids are used for the treatment of laryngitis in vocal performers and other individuals despite the absence of evidence demonstrating their impact on vocal fold inflammation. Our objective was to examine laryngeal secretion cytokine inflammatory profile changes associated with corticosteroid treatment in a human phonotrauma model. STUDY DESIGN: Prospective, individual, randomized, double-blinded, controlled trial. METHODS: Participants included 10 healthy females who were randomized to either treatment with oral hydrocortisone or placebo, each given in three doses over 20 hours after the experimental induction of acute phonotrauma. Cytokines associated with inflammation and healing (interleukin [IL]-1ß, IL-6, IL-10) were measured in laryngeal secretions before and after vocal loading and at 4 and 20 hours after treatment. RESULTS: Proinflammatory mediators IL-1ß and IL-6 were doubled in the controls versus the steroid treatment group at 21 hours following induction of acute vocal fold inflammation. Anti-inflammatory cytokine IL-10 showed a 6.3-fold increase in the steroid treatment group versus the controls, indicating anti-inflammatory modulation by steroid treatment. CONCLUSIONS: This study provides biologic evidence supporting the use of steroids for acute vocal fold inflammation associated with phonotrauma. LEVEL OF EVIDENCE: 1b.

Salivary concentration of epidermal growth factor in adults with reflux laryngitis before and after treatment.

OBJECTIVES: The diagnosis of laryngopharyngeal reflux (LPR) is controversial. There is no correlation between the number of reflux episodes and the severity of the inflammatory response at the esophagus or the laryngopharyngeal segment. Some authors have suggested that decreased salivary epidermal growth factor (EGF) concentrations in patients with gastroesophageal reflux disease and LPR point to a breakdown in the local defenses. Our objective was to establish whether treatment of the disease influences low salivary EGF concentrations. METHODS: The spontaneous whole saliva of 20 adults with LPR was sampled at a tertiary teaching hospital before and after a 16-week course of full-dose proton pump inhibitor and compared to that of 12 healthy controls. Salivary EGF concentrations were established with a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Although the mean salivary EGF concentrations were higher before treatment than after treatment and control of the disease (25,083 versus 19,359 pg/mL), this difference was not statistically significant (p = 0.065). The mean salivary EGF concentration of healthy control subjects was significantly higher (54,509 pg/mL; p < 0.0001). CONCLUSIONS: Both before and after treatment, patients with reflux laryngitis present lower salivary EGF concentrations than healthy control subjects, suggesting a primary deficit in their protective mechanisms.

Acid suppression does not reduce symptoms from vocal cord dysfunction, where gastro-laryngeal reflux is a known trigger.

Vocal cord dysfunction (VCD) is characterized by paradoxical inspiratory abduction of the vocal cords. Gastro-oesophageal reflux disease (GORD) is a known trigger. We studied 77 patients referred to a tertiary VCD clinic. VCD was diagnosed in 62, of which 83.9% had proven GORD. Following 8 weeks of acid suppression, 24.2% reported improvement in the severity and frequency of VCD attacks. This study suggests that empirical treatment of GORD in VCD marginally improves symptom control.

Vocal exercise may attenuate acute vocal fold inflammation.

OBJECTIVES/HYPOTHESES: The objective was to assess the utility of selected "resonant voice" (RV) exercises for the reduction of acute vocal fold inflammation. The hypothesis was that relatively large-amplitude, low-impact vocal fold exercises associated with RV would reduce inflammation more than spontaneous speech (SS) and possibly more than voice rest. STUDY DESIGN: The study design was prospective, randomized, and double blind. METHODS: Nine vocally healthy adults underwent a 1-hour vocal loading procedure, followed by randomization to a SS condition, vocal rest condition, or RV exercise condition. Treatments were monitored in clinic for 4 hours and continued extraclinically until the next morning. At baseline (BL), immediately after loading, after the 4-hour in-clinic treatment, and 24 hours post-BL, secretions were suctioned from the vocal folds bilaterally and submitted to enzyme-linked immunosorbent assay to estimate concentrations of key markers of tissue injury and inflammation: interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor α, matrix metalloproteinase (MMP)-8, and IL-10. RESULTS: Complete data sets were obtained for three markers--IL-1ß, IL-6, and MMP-8--for one subject in each treatment condition. For these markers, results were poorest at 24-hour follow-up in the SS condition, sharply improved in the voice rest condition, and was the best in the RV condition. Average results for all markers and responsive subjects with normal BL mediator concentrations revealed an almost identical pattern. CONCLUSIONS: Some forms of tissue mobilization may be useful to attenuate acute vocal fold inflammation.

Aquaporin changes in compound 48/80 induced inflammatory sublaryngeal edema in rat.

OBJECTIVES/HYPOTHESIS: Laryngeal edema is a common clinical condition. However, the underlying molecular mechanisms remain elusive. Aquaporins (AQPs) are small integral plasma membrane proteins that transport water across the plasma membrane. In this study, we explore the relationship between inflammatory laryngeal edema induced by compound 48/80 and the expression of AQPs. STUDY DESIGN: Prospective, controlled, experimental animal study. METHODS: Healthy adult male SD rats were injected with either sterile water, compound 48/80 (2 mg/kg), or compound 48/80 plus dexamethasone (3 mg/kg) via the tail vein. The larynxes were harvested 10, 30 minutes, and 1 hour after the injection for the measurement of sublaryngeal water content and histological and molecular evaluations. RESULTS: Ten and 30 minutes after the compound 48/80 injection compared with the sterile water injection control groups, the water content in subglottic larynx increased significantly and the tissues were markedly swollen accompanied with inflammatory cell infiltration. AQP1 and AQP5 mRNA decreased significantly. One hour after the compound 48/80 injection, the edema was diminished, but the inflammatory cell infiltration remained. AQP1 was elevated but AQP5 was still lower than controls. Dexamethasone did not significantly reduce laryngeal edema, but significantly reduced inflammatory cells infiltration induced by compound 48/80 injection. Dexamethasone increased the AQP5 level but not AQP1. CONCLUSIONS: AQP1 and AQP5 might play key roles in inflammatory subglottic edema caused by compound 48/80 in rats. AQP1 and AQP5 might be useful molecular targets of clinical treatment of inflammatory laryngeal edema.

[Comparison between conventional ph measurement and multichannel intraluminal esophageal impedance in children with respiratory disorders]. / Comparación entre pH-metría convencional e impedanciometría intraluminal multicanal en niños con patología respiratoria.

INTRODUCTION: Gastroesophageal reflux (GER) is associated with respiratory symptoms. The link between non-acid GER and the pathogenesis of respiratory disease has been demonstrated. Esophageal multichannel intraluminal impedance (MII) is able to detect non-acid and alkaline GER, as well as reflux height. The objective of the study was to compare the diagnostic effectiveness of dual-channel pH-meter and MII. PATIENTS AND METHODS: A prospective study was conducted on patients diagnosed with uncontrolled asthma, persistent cough, or chronic laryngitis. Patients were monitored continuously for 24 hours using a combination of MII and a dual-channel pH-meter. A descriptive and comparative analysis of the techniques was performed using the t test for comparison between groups and McNemar test for non-parametric data. RESULTS: A total of 49 patients with respiratory disease between September 2008 and April 2010 (79.6% uncontrolled asthma, 10.2% persistent cough, and 10.2% chronic laryngitis) were included in the study. The mean number of refluxes detected was 18.3 (range 0-93) using the pH-meter and 39.2 (11-119) using MII (P<.001). Acid GER was detected using pH in 7 children and using MII in 25 children (8 acid, 10 alkaline and 7 mixed). A mean of 21 proximal refluxes were detected using MII. CONCLUSIONS: MII makes it possible to diagnose a greater number of refluxes, whether acid or alkaline, than conventional pH measurement in children with respiratory disease that is poorly controlled with their usual treatment. MII can also detect proximal refluxes.

Can bile acids be an etiological factor for laryngeal carcinoma?

PURPOSE: The objective of this study is to show the accumulation of bile acids in laryngeal tissues of laryngeal carcinoma patients. MATERIALS AND METHODS: The present study compared the total bile acid level in the hypopharyngeal tissue, tumor tissue, and blood of 21 primary laryngeal carcinoma patients (study group) to that in the hypopharyngeal tissue and blood of 15 patients with benign laryngeal lesions (control group). RESULTS: The total bile acid level was significantly higher in the tumor and hypopharyngeal tissues of the study group than in the hypopharyngeal tissues of the control group; however, the difference in the blood total bile acid level between the 2 groups was not significant. CONCLUSION: Bile acids in reflux material accumulate in the laryngeal tissue in laryngeal carcinoma patients; therefore, bile acids should be considered a carcinogenic factor in the etiology of laryngeal carcinoma because of their mutagenicity due to DNA breaking, as they cause chronic inflammation due to intracellular accumulation.

[Optimal diagnostic criteria of ENT manifestations of GERD].

BACKGROUND: GERD has a number of extraesophageal manifestations (EEM) such as ENT, pulmonary etc. 24-hours pH monitoring in distal esophagus is widely used to confirm the diagnosis but its cut-off values for the diagnosing of extraesophageal manifestations of GERD (for example ENT) are unknown. AIM: To evaluate the optimal cut-off values for mean pH, time pH < 4 a day in the proximal esophagus and number of high gastroesophageal refluxes (HGR) in regard to presence of extraesophageal manifestations of GERD. METHODS: Ninety one GERD patients (50 men, 41 women, 42.33 +/- 16.1 y.o.) were examined using dual-probe 24-hours pH monitoring. The proximal probe was placed in the upper 1/3 part of esophagus over the upper esophageal sphincter. To confirm the presence of ENT manifestations of GERD all the patients were examined by qualified ENT-specialist; special ENT tests (laryngoscopy, pharyngoscopy with cytology and bacteriology) were performed. Toxic, allergic and infectious etiology of ENT were exclusion criteria. ROC curve analysis was used to evaluate optimal cut-off values of pH-studies. The cut-off values were chosen by the optimal diagnostic sensitivity (DSp)/specificity (DSp) ratio. RESULTS: ENT diseases were found in 59 of all the examined patients (chronic pharyngitis in 79.66% of them). HGR was found in 76.27% of patients in ENT group and in 43.75% of controls (consisted of GERD patients without signs of ENT pathology, n = 32), p = 0.0026. Mean number of HGRs was higher in ENT group compared to controls: (M +/- s) 12.51 +/- 18.56 vs 2.84 +/- 7.11 respectively, p (Mann-Whitney U-test) = 0.0003. Mean pH levels in the proximal esophagus were lower in the ENT group: (M +/- m) 6.32 +/- 0.52 vs 6.58 +/- 0.42, p = 0.011. Mean time pH <4 in the proximal esophagus differed significantly between ENT and GERD patients without ENT: 3.19 +/- 6.76 min in ENT group compared to 2.42 +/- 10.02 min in controls, p = 0.003. The calculated cut-off values for the number of high GER were 2 (DSn 71.19%, DSp 68.75%) or 3 (DSn = 61.02%, DSp = 71.88%); for mean pH in the proximal esophagus--6.3 (DSn = 75%, DSp = 51.47) or 6.4 (DSn = 68.75%, DSp = 58.82%); for time pH < 4--optimal value was 25 sec (DSn = 72.88%, DSp = 68.75%). CONCLUSIONS: Proximal pH monitoring may be useful in diagnosing extraesophageal manifestation of GERD. Optimal cut-off values of number of high GER are 2 to 3, mean pH 6.3-6.4 and time pH < 4 - 25 sec.

[Potentialities of the vegetative resonance test for diagnostics of hyperplastic processes in vocal folds].

The objective of the present study was to evaluate potentialities of the vegetative resonance test (VRT) for the elucidation of metabolic aspects of the inflammatory process in different forms of chronic vocal fold hyperplasty. The proposed diagnostic criteria characterize the inflammatory process in the larynx, specific features of metabolism in patients presenting with catarrhal and oedematopolypous laryngitis, characteristic changes in oedematofibrous and fibrous polyps. The use of VRT allowed diagnostic criteria for precarcinogenic conditions in the larynx to be developed.

[Tissue reactions of the laryngeal mucous membrane and its regulatory structures in experimental chronic laryngitis].

Experimental chronic laryngitis (ECL) was induced in 34 adult male rabbits by placement of fosta nylon thread into their trachea. Changes in the laryngeal mucous membrane in ECL were studied at days 30-90 using histological, histochemical and morphometric methods. ECL resulted in the thickening of both the epithelium and lamina propria of the laryngeal mucous membrane. In the ECL dynamics, the thickness of stratified squamous epithelium was increased insignificantly, however, it demonstrated the stimulation of the focal hyperplastic processes. Lamina propria, underlying this epithelium, was found to become thicker throughout the whole experiment (days 30-90). At the same time, progressive growth of the thickness of both pseudostratified ciliated epithelium and the lamina propria beneath was observed. This was accompanied by the hyperplasia of laryngeal endocrine cells and the increase of their secretory activity.

Inflammatory cytokine response to injury in the aging rabbit subglottis.

OBJECTIVES: We performed a pilot study to determine whether there is an age-related change in inflammatory expression in the subglottic mucosa of rabbits in response to a one-time injury. METHODS: Twenty-seven rabbits of 3 different ages meant to represent infant, adolescent, and adult stages underwent a unilateral, subglottic soft tissue injury. The animal groups were allowed to heal for 3 different durations to reflect the early, middle, and late stages of inflammation. Animal subglottises were then analyzed for quantitative differences in thickness and expression of multiple inflammatory cytokines within the soft tissue relative to the uninjured side. RESULTS: The animals in the youngest age group demonstrated a thickened-tissue response to injury yet a lower level of inflammatory cytokines than did the older animals at the early and middle stages of healing. CONCLUSIONS: Pronounced tissue thickness was an unanticipated finding in the youngest age groups and suggests better regulatory control by older animals. Also, a developmental difference in the inflammatory response to injury is suggested by the data.

Lipid laden macrophage indices and reflux finding score in canine gastroesophageal reflux model.

UNLABELLED: Laryngeal exposure to acid and aspiration of gastric contents may lead to severe respiratory disorders. This study utilizes the canine model of Gastroesophageal reflux (GER) to identify whether lower esophageal dysfunction is associated with upper and lower airway pathology. MATERIALS AND METHODS: Five mongrel dogs underwent GER-creating surgery (partial cardiomyectomy). Laryngeal reflux finding score (RFS), lipid-laden macrophage index (LLMI) and BAL fluid cell differential were obtained before and after surgery. RESULTS: Partial cardiomyectomy in dogs significantly increased the Reflux index (RI) from 0.38 +/- 0.21% to 7.56 +/- 2.89% (P = 0.048), the duration of the longest reflux episode (DLRE) from 1.22 +/- 1.19 min to 66.2 +/- 42.03 min postoperatively (P = 0.049) and the total number of episodes in 24 hr from 2.06 +/- 1.03 to a postoperative value of 19.24 +/- 4.79. There was no statistically significant change in values for RFS, LLMI, and BAL fluid cell differential after the induction of GER. CONCLUSIONS: Acid reflux to the proximal esophagus of this animal model did not cause laryngeal exposure to acid or aspiration of gastric content. The results of this study suggest that presence of GER, secondary to lower esophageal dysfunction is not necessarily associated with upper and lower airway pathology.

Salivary egf concentration in adults with reflux chronic laryngitis before and after treatment: preliminary results.

UNLABELLED: The Laryngopharyngeal Reflux (LPR) physiopathology is still unknown. The Epidermal Growth Factor (EGF) is a biologically active salivary protein that aids in the rapid regeneration of the oropharyngeal and upper digestive tract mucosas. Salivary deficiency of this protein in patients with LPR has been demonstrated in previous studies. AIM: To compare salivary EGF concentration in patients with LPR before and after treatment. MATERIALS AND METHODS: In this prospective study twelve patients with GERD and moderate LPR were studied. Whole saliva samples were collected before and after treatment and salivary EGF concentration was determined using a commercially available ELISA kit (Quantikine). RESULTS: There were eleven females and one male among the patients, the mean age was 49 years. The mean pre-treatment salivary EGF concentration was 2,867.6 pg/mL and the mean post treatment EGF concentration was 1,588.5 pg/mL. This difference was statistically significant (p=0.015). DISCUSSION AND CONCLUSIONS: Although salivary EGF concentrations are higher before LPR treatment, the concentration is still much lower than the mean salivary EGF concentration in normal individuals without LPR, which suggests a primary disorder of this defense factor in individuals with LPR.