The mucosal immune response to laryngopharyngeal reflux.

RATIONALE: Laryngopharyngeal reflux (LPR) affects up to 20% of Western populations. Although individual morbidity is usually moderate, treatment costs are high and there are associations with other diseases, including laryngeal cancer. To date, there have been no studies of the mucosal immune response to this common inflammatory disease. OBJECTIVES: To determine the mucosal immune response to LPR. METHODS: We performed a prospective immunologic study of laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11, respectively), and of primary laryngeal epithelial cells in vitro. MEASUREMENTS AND MAIN RESULTS: Quantitative multiple-color immunofluorescence, using antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68, EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II), and classical and nonclassical MHC (I, II, beta(2)-microglobulin, CD1d). Univariate and multivariate analysis and colocalization measurements were applied. There was an increase in percentage area of mucosal CD8(+) cells in the epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were unchanged. Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01). CONCLUSIONS: These data indicate a role for the CD1d-NKT cell axis in response to LPR in humans. This represents a useful target for novel diagnostics and treatments in this common condition.

Laryngopharyngeal reflux: diagnosis and treatment of a controversial disease.

PURPOSE OF REVIEW: Laryngopharyngeal reflux is a well-recognized and widely used term in ear, nose and throat practice. However, the symptoms and signs attributed to laryngopharyngeal reflux are non-specific and treatment is usually empirical. This review discusses current knowledge on diagnosis and treatment of laryngopharyngeal reflux. RECENT FINDINGS: Information is evolving regarding the implications of laryngopharyngeal reflux in the development of pathological conditions affecting the upper aerodigestive tract epithelium such as chronic laryngitis, otitis media with effusion and chronic sinusitis. However, there is still much to learn about the pathophysiologic mechanisms of laryngopharyngeal reflux and their role in its related disease conditions and there is still considerable controversy on diagnostic as well as therapeutic parameters for this condition. There is no consensus on the diagnosis and treatment of laryngopharyngeal reflux and the majority of clinicians depend mainly on clinical findings and empirical therapeutic tests rather than more specific investigations. SUMMARY: The concept of laryngopharyngeal reflux is still controversial. The current practice of empirical treatment with proton-pump inhibitors is based on weak evidence. However, this practice seems to be widely accepted and will not change until further clinical and laboratory studies improve our understanding of this common and well-recognized condition.

[Dendritic cells, T- and B-lymphocytes and macrophages in supraglottic and glottic squamous epithelial carcinoma. Location and correlation with prognosis of the illness]. / Dendritische Zellen, T-und B-Lymphozyten und Makrophagen im supraglottischen und glottischen Plattenepithelkarzinom. Lokalisation und Korrelation zur Prognose der Erkrankung.

Dendritic cells play an important role within the mucosal immune system of the upper aerodigestive tract. They process exogenous and endogenous antigens and are able to induce a cytotoxic Tc/s lymphocyte reaction against tumors. Recently published data indicate that the in vitro application of tumor lysate incubated dendritic cells can provide a defense against melanoma. Before these new therapeutic strategies are available for the therapy of laryngeal cancer, basic studies have to be performed concerning the distribution of dendritic cells and other subpopulations, such as T- and B-lymphocytes and macrophages. In the present study the distribution of these subpopulations were examined within the epithelial and connective tissue compartments ("tumor front") of 20T2 squamous cell carcinomas of the supraglottis and glottis. The number of dendritic cells was compared with clinical parameters to check whether a high number of dendritic cells could be correlated with a better prognosis. In contrast to T-lymphocytes, results showed that dendritic cells were mainly located within the epithelial compartment of the tumors, their number ranging from 20 cells/mm2 to > 700 cells/mm2. By comparing each patient's clinical course with the number of dendritic cells, findings showed that those patients who died within the first postoperative year were characterized by a very small number of dendritic cells within their tumor tissue (< 100 cells/mm2). Although the number of patients was low, results indicate that a high number of dendritic cells within tumor tissue suggest a better prognosis.

Langerhans cells in the larynx and the hypopharynx.

Langerhans cells are important in the human immune system as a part of the dendritic cell system. This study was carried out to demonstrate the presence of Langerhans cells and their distribution in normal human larynx and hypopharynx, by light (S-100 polyclonal antibody) and transmission electron microscopy. The results are summarized as follows: 1) Langerhans cells with cytoplasmic granules (Langerhans granules or Birbeck's granules) were situated in the suprabasal region of the squamous epithelium in the larynx and the hypopharynx. 2) They distributed in the membranous portion of the vocal folds, epiglottis, aryepiglottic folds, arytenoid regions and interarytenoid notch of the larynx. The cells surrounded the vestibule and glottis of the larynx. 3) They distributed in the postcricoid area, piriform sinus and posterior pharyngeal wall of the hypopharynx. The cells were situated above the entrance of esophagus. 4) The cells were suggested to be a factor of immune response at the entrance of trachea and esophagus.