[Influence of TNF-α on the immunomodulatory property of laryngeal mucosa mesenchymal stromal cells'].

Objective: To investigate the effect of tumor necrosis factor-alpha(TNF-α)on the immunoregulatory capacity of laryngeal mucosal mesenchymal stromal cells (LM-MSCs) and its potential molecular mechanism, and provide a theoretical basis for the study of chronic laryngitis. Methods: LM-MSCs were separated from epiglottal mucosa. The LM-MSCs cells were directly co-cultured with T cells in vitro to detect the immunomodulatory property of LM-MSCs. After long-term stimulation with inflammatory factors TNF-α in vitro, the differences were compared in the immunomodulatory ability of LM-MSCs between normal LM-MSCs and TNF-α stimulated LM-MSCs. The expression of general control non-repressed protein5(GCN5), FAS, FASL in normal LM-MSCs and TNF-α stimulated LM-MSCs was detected by Western blot and quantitative real-time RT-PCR(RT-qPCR). Results: After chronic stimulation of TNF-α, the RNA relative expression of GCN5 was 0.31±0.03 (3 days) and 0.53±0.06 (7 days) compared with control group, showing significant difference (F=13.45, P<0.05). The percentage of LM-MSC-induced T cell apoptosis was 6.27%±0.81% (3 days) and 4.99%±0.52% (7 days) in chronic stimulation group compared with control group 10.02%±1.02%. There is a significant difference among these groups (F=11.13, P<0.05). Moreover, the ability of LM-MSCs to induce T cell apoptosis is regulated by GCN5. Conclusion: With the chronic stimulation of TNF-α, the expression of GCN5 in LM-MSCs is decreased, thus impairing its immunoregulatory capacity.

[The problems associated with the treatment of stenosing laryngotracheitis in the children (the results of the 35 year-long experience)]. / Problemy lecheniia stenoziruiushchego laringotrakheita u detei (rezul'taty 35-letnego opyta).

Stenosing laryngotracheitis (SLT) affecting the children is considered to be an emergency pediatric condition associated with ENT pathology. Its treatment presents a serious challenge for otolaryngologists, pediatricians, specialists in communicable diseases, allergologists, etc. We have undertaken a retrospective analysis of the available data with a view to summarizing the tendencies in the evolution of SLT morbidity. The results of the 35 year-long experience with the use of the currently available therapeutic strategies for the treatment of the children suffering from stenosing laryngotracheitis are presented. Special emphasis is laid on the advantages of the combined treatment of the patients presenting with this condition based at a specialized infectious department with the participation of an otorhinolaryngologist.

Allergic laryngitis: unraveling the myths.

PURPOSE OF REVIEW: This article provides a thorough review of the literature highlighting the articles that have advanced our knowledge about the sensitivity of the larynx to allergens in the air or ones consumed. This area of inquiry requires continued interest and investigation. As the field of clinical laryngology changes, and more information is discovered about the possible causal association between allergy and vocal pathologies, practicing otolaryngologists, allergists, and other medical professionals may discover more comprehensive methods to evaluate and treat their allergic patients, particularly those who present with complaints of dysphonia, dysphagia, laryngopharyngeal reflux (LPR), and/or dyspnea. RECENT FINDINGS: There continues to be epidemiological studies designed to describe the relationship of allergy to vocal symptoms and signs. Both population and smaller studies have recently attempted to link these two conditions. Unfortunately, the patient with chronic laryngeal complaints is often tagged by default with the diagnosis of LPR and treated with proton pump inhibitors, which are not always beneficial. The endoscopic assessment may not be as reliable to make the diagnosis of LPR as the examination is subjective and the inter-rater reliability is low. It has been demonstrated by direct laryngeal provocation studies that sticky-viscous endo-laryngeal mucous is the only reliable finding consistently associated with allergy potential allergic tissue reactivity. SUMMARY: The interrelationship of allergic sensitivity and chronic laryngitis in certain individuals is becoming clearer because our knowledge of inquiry has increased and the available routine technology to diagnose these conditions has remarkably improved. Notwithstanding these advancements, much more research is needed on this subject to reduce the frequency of mis-diagnoses and mis-management of allergic patients.

Invasive fungal laryngopharyngitis resulting in laryngeal destruction with complete laryngotracheal separation: Report of a case.

As the treatment of hematopoietic cancers evolves, otolaryngologists will see a higher incidence of opportunistic infections. We discuss a case of invasive fungal disease that invaded the larynx, pharynx, trachea, and pulmonary parenchyma after chemotherapy. The patient, a 46-year-old woman, presented 1 week after undergoing induction chemotherapy. Her initial symptoms were odynophagia and dysphagia. Despite encouraging findings on physical examination, her health rapidly declined and she required an urgent tracheotomy and multiple operations to address spreading necrosis. Because of her inability to heal, she was not a candidate for laryngectomy, so she was treated with conservative management. The patient was then lost to follow-up, but she returned 5 months later with laryngeal destruction and a complete laryngotracheal separation. While noninvasive fungal laryngitis is routinely encountered, its invasive counterpart is rare. The literature demonstrates that some cases completely resolve with medical therapy alone but that surgery is necessary in others. We recommend surgical debridement of all necrotic tissue.

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.

[Cytokine profile in young children with acute stenotic laryngotracheitis].

INTRODUCTION: One of the most severe complications of acute respiratory infections in young children is acute stenotic laryngotracheitis (croup). The relationship between cytokine blood levels and symptoms of croup, croup severity, disease sequel, despite numerous studies is still unclear. AIM: Cytokine profile in young children with acute stenotic laryngotracheitis investigation. MATERIAL AND METHODS: 112 children aged 12 min. - 36 mon. with acute stenotic laryngotracheitis which were treated at the Lviv Regional Infectious Diseases Hospital were kept under observation. Croup symptoms, levels of interleukins (IL1, IL4, IL6, IL10, IL17) in serum, DNA and RNA viruses in respiratory nasal mucus were studied; Chan croup severity was used. RESULTS: In the pathogenesis of croup has an important role the imbalance between inflammatory (IL1, IL6) and anti-inflammatory (IL4, IL10, IL17) cytokines, which does not reduce the intensity of inflammatory reactions and its lead to local swelling, muscle spasm, excessive production of mucus in the place of viral replication. The levels of inflammatory and anti-inflammatory cytokines in the blood serum of children with croup were significantly higher than in patients with acute laryngitis. In patients with recurrent croup, unlike patients with the first case of croup does we don't see a significant correlation between the concentrations of inflammatory and anti-inflammatory cytokine levels Conclusions: The significantly higher levels of cytokines in children with croup compared with the group of patients with acute laryngitis were found, imbalance between anti-inflammatory (IL1, IL6) cytokine levels and inflammatory (IL4, IL10, IL17) cytokine levels in children who developed recurrent croup.

Laringitis fúngica en pacientes inmunocompetentes / Fungal laryngitis in immunocompetent patients

Introducción: La laringitis fúngica es una patología poco planteada en pacientes inmunocompetentes, sin embargo se debería tener en consideración en el diagnóstico diferencial de leucoplaquias en estos pacientes, más aún con factores predisponentes como reflujo faringolaríngeo, tabaquismo crónico y/o uso de corticoides. Objetivo: Presentar una serie de casos de pacientes inmunocompetentes con diagnóstico clínico de laringitis fúngica y tratamiento antimicótico empírico. Describir la asociación con factores predisponentes claves. Material y método: Estudio retrospectivo que incluyó a 11 pacientes con diagnóstico clínico de laringitis fúngica por correlación de la clínica, factores predisponentes y hallazgos en la videoestroboscopía laríngea (leucoplaquias múltiples en los pliegues vocales) sumado a la respuesta a tratamiento empírico con fluconazol oral. Se realizó además una revisión de la literatura disponible hasta el año 2015. Resultados: Todos los diagnósticos fueron clínicos correlacionando síntomas con hallazgo de leucoplaquias características en la laringe. El principal factor asociado fue el reflujo faringolaríngeo (91%) seguido por uso de corticoides (55%). Todos los pacientes fueron tratados con un esquema empírico de fluconazol oral por 14-21 días. El 100% de los pacientes respondió de forma exitosa al uso de este fármaco con remisión de los síntomas y de las lesiones laríngeas. Conclusión: El diagnóstico clínico y tratamiento con fluconazol oral como tratamiento de primera línea generarían buena tasa de respuesta, siempre que se correlacionen los síntomas y signos del paciente con los hallazgos encontrados en la laringe.

Introduction: The fungal laryngitis is an unusual disease in immunocompetent patients, however should take into consideration in the differential diagnosis of leukoplakias, especially in patients with predisposing factors such as pharyngolaryngeal reflux, use of inhaled, oral or intravenous corticosteroids. Aim: Describe a series of cases of fungal laryngitis in immunocompetent patients with clinical diagnosis and empirical antifungal treatment. In addition, finding the association with predisposing factors keys. Material and method: Retrospective study of 11 patients with diagnosis of fungal laryngitis according to clinical presentation, predisposing factors and findings in the laryngeal videostroboscopy (vocal folds leukoplakias) joined the response to empirical treatment with oral fluconazole. Also an extensive literature review was conducted until 2015. Results: The main predisposing factor was the pharyngolaryngeal reflux (91%) followed by use of corticosteroids (55%). All patients were treated empirically with fluconazole for 14-21 days. 100% of patients responded successfully, with remission of symptoms and laryngeal lesions. Conclusion: Clinical diagnosis and treatment with fluconazole as first-line treatment generate good response rate, provided that the patient's symptoms and signs with the findings in the larynx are correlated.

Utility of Allergy Testing in Patients with Chronic Laryngopharyngeal Symptoms: Is It Allergic Laryngitis?

OBJECTIVE: To determine the utility of allergy evaluation in patients with chronic refractory laryngeal symptoms. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic medical center. SUBJECTS: All patients who underwent in vitro allergy testing at a single institution from 2006 to 2010, for a total of 998 patients. METHODS: Charts of patients who underwent in vitro allergy testing were identified. The charts were reviewed for the primary indication for allergy testing, as categorized into rhinitis complaints, chronic sinusitis, otitis media, and refractory laryngeal symptoms (globus, cough, throat clearing, increased secretions, and hoarseness). Results of allergy tests and comorbid conditions were analyzed and compared among groups. RESULTS: The positive yield of allergy testing in patients with primary laryngeal indications was 51.8%, 63.3% for rhinitis, 60.9% for sinusitis, and 33.3% for otitis media. The odds ratio of having a positive test was not statistically different for patients with laryngeal symptoms, rhinitis, or sinusitis. Patients with chronic laryngeal symptoms and positive allergy testing were most often sensitized to dust mites (63%) and least often sensitized to molds (1.3%). CONCLUSIONS: Allergy testing in patients with chronic laryngeal symptoms yields positive results in equivalent proportion to patients with other common presenting symptoms. Dust mites sensitization is the most common sensitization in patients with allergic laryngitis.

Soot and house dust mite allergen cause eosinophilic laryngitis in an animal model.

OBJECTIVES/HYPOTHESIS: Chronic laryngitis (CL) is common and costly. One of the most common causes of CL is thought to be laryngopharyngeal reflux, although a significant percentage of individuals fail to get better with acid suppressive therapy. The role of other potential causes of CL such as allergy and environmental pollution has not been thoroughly investigated. PURPOSE: To evaluate the association between iron soot, house dust mite allergen (HDMA), and CL in an established animal model. METHODS: Twenty-four guinea pigs were separated into four 6-week exposure groups: 1) saline (allergen control) + filtered air (pollution control); 2) HDMA (Dermatophygoides farinae) + filtered air; 3) saline + combustion particulates; or 4) HDMA + combustion particulates. The primary outcome measure was mean eosinophil profile (MEP) in glottic, subglottic, and trachea epithelium and submucosa. RESULTS: The combination of iron soot and HDMA caused eosinophilia (elevated MEP) in the glottic (P < 0.06), subglottic (P < 0.05), and trachea (P < 0.05) submucosa and epithelium (P < 0.05). CONCLUSION: The combination of HDMA and iron soot resulted in laryngeal eosinophilia in an established guinea pig model of CL. The data support the notion that factors other than reflux may cause CL. Further investigation into eosinophilic laryngitis as a distinct clinical entity caused by exposure to environmental allergen and pollution is warranted.

Primary laryngeal cryptococcosis resembling laryngeal carcinoma.

A case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. Histological examination showed pseudoepitheliomatous hyperplasia and severe submucosal inflammation with ovoid budding yeasts by Grocott's stain. A serological study indicated a high titer of cryptococcal antigen. After treating with oral fluconazole for 3 months, her primary lesion of larynx turned to be clear. We implicate a long-term use of steroids as the significant risk factor in developing cryptococcosis of the larynx.

[SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study.

An in vivo study of composite microgels based on hyaluronic acid and gelatin for the reconstruction of surgically injured rat vocal folds.

PURPOSE The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. METHOD Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 µl saline (placebo controls), HA-bulk, or HA-Ge hydrogel was injected into the lamina propria (LP) 5 days after surgery. The vocal folds were harvested at 3, 14, and 28 days after injection and analyzed using hematoxylin and eosin staining and immunohistochemistry staining for macrophages, myofibroblasts, elastin, collagen type I, and collagen type III. RESULTS The macrophage count was statistically significantly lower in the HA-Ge group than in the saline group (p < .05) at Day 28. Results suggested that the HA-Ge injection did not induce inflammatory or rejection response. Myofibroblast counts and elastin were statistically insignificant across treatment groups at all time points. Increased elastin deposition was qualitatively observed in both HA groups from Day 3 to Day 28, and not in the saline group. Significantly more elastin was observed in the HA-bulk group than in the uninjured group at Day 28. Significantly more collagen type I was observed in the HA-bulk and HA-Ge groups than in the saline group (p < .05) at Day 28. The collagen type I concentration in the HA-Ge and saline groups was found to be comparable to that in the uninjured controls at Day 28. The concentration of collagen type III in all treatment groups was similar to that in uninjured controls at Day 28. CONCLUSION Local HA-Ge and HA-bulk injections for acute injured vocal folds were biocompatible and did not induce adverse response.

Effects of Gan lian Yu ping feng powder on the antibody titers to infectious laryngotracheitis vaccine and some nonspecific immune indexes in chickens.

The study was conducted in order to investigate the immuno-enhancing property of the Chinese herbal formula, Gan lian Yu ping feng powder. Three hundred and thirty six 45-day-old chicks were randomly divided into eight groups. The chicks in groups A, B, C were orally given 0.25 g/mL (low-), 0.5 g/mL (middle-) and 1.0 g/mL (high) dose of Gan lian Yu ping feng powder in the drinking water respectively for 3 days consecutively. They were then immunised with infectious laryngotracheitis vaccine (ILTV) on the 4th day. Groups D, E, F were given 0.25 g/mL, 0.5 g/mL and 1.0 g/mL dose of Gan lian Yu ping feng powder respectively after the immunisation for three days consecutively. Group G was Wen du qing (a government approved herbal product for ILT) control group, and group H was blank control group. At 52, 59, 73, 87 days of age, 8 chicks of each group were selected randomly for blood sampling to determine the levels of IFN-γ, IL-4 and the antibody of ILT. Then the chickens were sacrificed, with the thymus, spleen and Bursa of Fabricius being weighed for the calculation of immune organ indexes. The results showed that high and middle dosages of Gan lian Yu ping feng powder given at the day before immunisation and 3 days after immunisation elevated not only the contents of IFN-γ, the antibody titers of ILT (P<0.01) and the immune organ indexes (P<0.05) significantly, but also reduced the contents of IL-4. There was a significantly different degree of enhancement in the content of IFN-γ, the antibody of ILT (P<0.01) and the immune organ index (P<0.05). The results indicate that Gan lian Yu ping feng powder effectively improves the immunity in chickens.

[Cycloferon in therapy of hyperplastic laryngitis for decrease of the number of relapses].

The article describes the clinical forms of chronic hyperplastic laryngitis, characterized by persistent and recurrent course, a tendency to the formation of oncological pathology, at the expense of hyperplastic changes in the larynx, leading to a malignancy of the inflammatory process. It was demonstrated the bacterization of larynx by Epstein-Barr virus (EBV) and Mycoplasma in imbalance of system of interferon. Clinical recovery, depending on the clinical form of the disease, using cycloferon, was observed in 57.4% of patients. The inclusion in the complex of the medical support of chronic hyperplastic laryngitis inducer of interferon - cycloferon, provided the reduction of the number of relapses.

Potentiated anti-inflammatory effect of combined 780 nm and 660 nm low level laser therapy on the experimental laryngitis.

Reflux laryngitis is a common clinic complication of nasogastric intubation (NSGI). Since there is no report concerning the effects of low level laser therapy (LLLT) on reflux laryngitis, this study aimed to analyze the protective effect of single and combined therapies with low level laser at the doses of 2.1J and 2.1+1.2 J with a total irradiation time of 30s and 30+30 s, respectively, on a model of neurogenic reflux laryngitis. NSGI was performed in Wistar rats, assigned into groups: NGI (no treatment), NLT17.5 (single therapy), and NLT17.5/10.0 (combined therapy, applied sequentially). Additional non-intubated and non-irradiated rats were use as controls (CTR). Myeloperoxidase (MPO) activity was assessed by colorimetric method after the intubation period (on days 1, 3, 5, and 7), whereas paraffin-embedded laryngeal specimens were used to carry out histopathological analysis of the inflammatory response, granulation tissue, and collagen deposition 7 days after NSGI. Significant reduction in MPO activity (p<0.05) and in the severity of the inflammatory response (p<0.05), and improvement in the granulation tissue (p<0.05) was observed in NLT17.5/10.0 group. Mast cells count was significantly decreased in NGI and NLT17.5 groups (p<0.001), whereas no difference was observed between NLT17.5/10.0 and CTR groups (p>0.05). NLT17.5/10.0 group also showed better collagenization pattern, in comparison to NGI and NLT17.5 groups. This study suggests that the combined therapy successfully modulated the inflammatory response and collagenization in experimental model of NSGI-induced neurogenic laryngitis.

[Cycloferon in complex therapy management of chronic laryngitis].

The clinical course of various forms of chronic laryngitis, including contact granulomas not only persistant and relapsing, but also inclined to oncologic pathology due to hyperplastic changes in the larynx resulting in malignization was described. Inhibition of the leukocyte interferon-synthesizing activity was observed in more than 88.1% of the subjects. Pathogenic viruses were isolated from 48.2% of the patients, EBV and mycoplasma prevailing. High direct correlation between chronic laryngitis and Herpes viruses was shown. The presence of three-component virus associations in the larynx mucosa was likely indicative of the bening process malignancy. The use of the interferon inductor cycloferon in the complex surgical and medicamentous management of chronic laryngitis was shown valid. The rate of the relapses lowered to 1.7 episodes a year.

Methyl methacrylate and respiratory sensitization: a critical review.

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants. The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer.

[Recidivant laryngeal leishmaniasis: an unusual case in an immunocompetent patient treated with corticosteroids]. / Leishmaniosis laríngea recidivante: un caso inusual en un paciente inmunocompetente tratado con corticoides.

Leishmaniosis is a chronic parasitic disease, which in Argentina is mainly caused by protozoa belonging to the Leishmania (Viannia) braziliensis complex, leading to cutaneous and mucosal pathologies. We report a rare case of laryngeal leishmaniosis in a 29 year-old man from Jujuy province, Argentina, who had been misdiagnosed with other pathologies, carrying this infectious disease for about 20 years. During 2008, the patient was admitted with complaints of progressive hoarseness of the voice and dyspnea. He also reported having received tuberculostatics, antifungal and corticosteroids treatments since 2002. Different biopsies and direct laryngoscopic exams revealed inespecific granulomatous larynx, TBC-related laryngitis, laryngitis related to Histoplasma infection, extra-nodal Natural Killer-cell lymphoma. Finally, the patient was evaluated at the University Hospital and the final diagnosis was: granulomatous larynx, intra and extra-cytoplasmic Leishmania spp amastigotes, negative for TBC and Histoplasma cultures, and chronic laryngitis related to Leishmania infection, according to the laryngeal endoscopy, microbiological and histopathological exams, respectively. The patient received pentavalent antimonial treatment and his condition improved after 2 months of follow-up. Primary laryngeal leishmaniosis is rare and this localization does not belong to the most prevalent mucosal leishmaniosis. However, this parasitic disease warrants special concern, especially in patients who received prolonged corticosteroid treatments, in order to avoid a misdiagnosis of this disease.

The selective COX-2 inhibitor Etoricoxib reduces acute inflammatory markers in a model of neurogenic laryngitis but loses its efficacy with prolonged treatment.

OBJECTIVE: A randomised experimental study was used to evaluate the therapeutic effect of a selective cyclooxygenase-2 (COX-2) inhibitor in neurogenic laryngitis. MATERIALS AND METHODS: Male Wistar Han rats were subjected to the nasogastric intubation model (NGI) of laryngitis for 1 and 2 weeks. The NGI animals were divided into three groups: (1) treated with COX-2 inhibitor Etoricoxib, (2) vehicle and (3) non-intubated animals. A fourth group of animals was submitted to NGI only. Laryngeal sections were immunostained for substance P (SP) and calcitonin gene-related peptide (CGRP) fibre-immunoreactivity (IR) and quantification of COX-2 positive cells through stereological analysis. The expression of COX-2, interleukins IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha) was determined by quantitative real time QRT-PCR. TREATMENT: Etoricoxib (6 mg/kg/day) was prepared in 0.9% sterile saline with 5% glucose (vehicle) and administered daily during 1 or 2 weeks. RESULTS: Treatment for 1 week with Etoricoxib attenuated the CGRP-IR fibre depletion, the COX-2-IR increased cell number and the TNF-alpha and COX-2 mRNA increased levels induced by NGI. Two weeks of treatment had no beneficial effect. CONCLUSIONS: Etoricoxib is effective in neurogenic laryngitis for limited periods of administration, indicating that selective COX-2 inhibitors should be evaluated in the future.

Local production of inflammatory mediators during childhood parainfluenza virus infection.

OBJECTIVE: To describe the clinical manifestations of parainfluenza virus (PIV) infection and to characterize biochemical markers of PIV disease severity. PATIENTS AND METHODS: We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics. RESULTS: A total of 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. Fifty-two patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. Lower respiratory tract infection (LRTI) was diagnosed in 67 (44%) patients, 21 (14%) had laryngotracheobronchitis, and 49 (32%) had an upper respiratory infection other than laryngotracheobronchitis. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2, and 50% of those with PIV4. Compared with uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin-6, CX-chemokine ligand 8 (CXCL8 or interleukin-8), CCL3 (macrophage inflammatory protein-1alpha), CCL4 (macrophage inflammatory protein-1beta), CXCL9 (monokine induced by interferon gamma), and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and PIV 1 or 3 (respirovirus) infection had higher nasal wash concentrations of CXCL8 when compared with patients with upper respiratory infection, mild illness, or PIV 2 and 4 (rubulavirus) infection (P < 0.05). CONCLUSIONS: PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated concentrations of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease.