Inflamed Middle Ear Mucosa Research Articles

Intraoperative and postoperative findings in children with myringotomy tubes (MT) undergoing cochlear implantation (CI)

Objective To evaluate and compare children undergoing cochlear implantation (CI) with myringotomy tubes (MT) placed preoperatively or intraoperatively to those without MT . Methods This was a retrospective review of pediatric patients undergoing CI between 2015 to 2020 at a tertiary care pediatric hospital. CI patients with and without MT were reviewed for the following outcomes: intraoperative findings, intraoperative and postoperative complications, and surgical time. Descriptive and bivariable statistical analysis was performed. Results 192 cochlear implant surgeries were included: 116 without MT tubes and 76 with a history of MT. Twenty-six patients had MT present at the time of CI surgery. No statistical difference existed between patients with MT (CI + MT group) and those without MT (CI – MT group) with regard to intraoperative complications (P = 0.760) and intraoperative findings (P = 0.545). MT association with total post-operative complications (GEE) showed no statistical significance (OR 2.45, 95% CI 0.83–7.22, P-value 0.105). CI + MT patients were significantly more likely to have inflamed middle ear mucosa at time of surgery (P = 0.003). CI + MT patients did not have a longer length of surgery compared to the CI – MT group (3.47 h vs 3.3 h, respectively, P = 0.342). Conclusion Our data confirms it is safe to perform CI in ears with myringotomy tubes, although the surgeon should be aware of possibly encountering increased middle ear inflammation during the surgery.

Expression of tumor necrosis factor Alpha, interleukin-1 and matrix metalloproteinase-9 and pathomorphological changes in acquired middle ear cholesteatoma

<p>Introduction. The inflammatory mediators play a central role in the pathogenesis of the inflammatory process of the middle ear and cholesteatoma from the aspect of initiating and maintaining the inflammatory response to infection and lesion. The aim of the study was to examine if the presence of acquired cholesteatoma could predict pathomorphological changes of the tympanic cavity mucosa in relation to the control tissue of the inflamed middle ear mucosa and to examine and compare the expression levels of tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1) and matrix metalloproteinase 9 (MMP-9) with pathomorphological changes in the middle ear mucosa in chronic otitis media (COM), with and without acquired cholesteatoma (AC). Methods. The immunohistochemical study included 178 patients of both sexes, aged 5 to 75, who underwent microsurgical treatment of COM from 2015 to 2018. Patients were divided into two groups based on the presence or absence of AC of the middle ear: 97 with cholesteatoma (CCOM) and 81 without cholesteatoma (COM). Samples of the perimatrix of AC and inflamed middle ear mucosa were taken intraoperatively. The condition of the tympanic cavity mucosa was examined by otomicroscopy exploration intraoperatively. The expression levels of TNF-a, IL-1 and MMP-9 were determined by immunohistochemical analysis. Results. The difference in the percentage distribution of patients according to the condition of the tympanic cavity mucosa between both groups was statistically significant (p <0.01) where in the COM group the highest frequency was 43.2% of patients with mucosal hypertrophy, and in the CCOM 56.7% with granulations. With highly positive expression of TNF-R2 and IL-1, a higher probability of the presence of mucosal hypertrophy and granulations can be expected, and with highly positive expression of MMP-9 the presence of granulations. Conclusion. Acquired middle ear cholesteatoma is a statistically significant predictor of the occurence of mucosal hypertrophy and granulations in the tympanic cavity in relation to the control tissue of the inflamed middle ear mucosa. The high expression of TNF-R2, IL-1 and MMP-9 shows a statistically significant association with the presence of granulations and mucosal hypertrophy in acquired middle ear cholesteatoma which may have clinical significance in the evaluation and prognosis of the disease.</p>

Expression of matrix metalloproteinase-9 in acquired middle ear cholesteatoma

<p>Introduction. Matrix metalloproteinase-9 (MMP-9) plays one of the key roles in the migration of inflammatory cells and the destructive behavior of acquired middle ear cholesteatoma. The aim of the study was to determine the expression levels of MMP-9 in chronic otitis media, with and without acquired cholesteatoma, as well as to determine the correlation between them and the pathomorphological changes in the tympanic membrane (TM). Methods. Immunohistochemical study included 178 patients of both sexes, aged 5-75 years, who underwent microsurgical treatment of chronic otitis media (COM) at the Ear, Nose and Throat Department of the University Clinical Center of the Republic of Srpska in Banja Luka from 2015 to 2018. Patients were divided into two groups on the basis of the presence or absence of acquired cholesteatoma: 97 (CCOM) and 81 (COMWC). The samples of the perimatrix of acquired cholesteatoma (n=97) and inflamed middle ear mucosa (n=81) were taken intraoperatively. The presence of retraction and certain types and subtypes of TM perforations were examined by intraoperative exploration. MMP-9 expression levels were determined by immunohistochemical analysis. Results. In the presence of cholesteatoma and highly positive expression of MMP-9, the marginal type of TM perforation was more likely to occur (p<0.01) while in negative expression of MMP-9 in the COMWC group, the central type was more likely to occur (p<0.01). There was a higher probability of the presence of attic subtype of TM perforation in patients with cholesteatoma and moderate positive expression of MMP-9 (p<0.01). There was not a statistically significant contribution of any of the factors in the prediction of the influence on the occurrence of TM retraction. Conclusion. The presence of acquired middle ear cholesteatoma and highly positive expression of MMP-9 are statistically significant predictors of the presence of marginal type and attic subtype of TM perforation. Expression levels of MMP-9 may have potential clinical significance in the development of irreversible pathomorphological changes on TM in middle ear cholesteatoma.</p>

Expression of Interleukins (ILs) mRNA in Otitis Media

The purpose of this study was to investigate the expression of interleukins (ILs) cytokine in postauricular skin, mastoid mucosa, inflamed mastoid mucosa and middle ear mucosa from Otitis patients. Specimens were obtained from patients with otitis media who visited the Department of Otorhinolaryngology, Chungju Hospital, Kunkuk University School of Medicine, Chungju, Republic of Korea between August 2015 and July 2017. We examined human 38 kinds of human interleukins in this experiment. The total RNA was extracted from specimens using RNAiso Plus (Takara, Japan) according to the manufacturer's instructions. 38 ILs primers were used. IL-4, IL-8, IL-9, IL-21, IL-24 were not expressed at postauricular skin, mastoid mucosa, inflamed mastoid mucosa, and middle ear mucosa. IL-1a, IL-17, IL-17d, IL-17e and IL-17f were strongly expressed in mastoid mucosa and middle ear mucosa. The degree of IL-7 gene expression may be an indicator gene in otitis media. IL-1a, IL-17, IL-17d, IL-17e and IL-17f were involved in the inflammatory and immune processes of otitis media.

Recovery time for inflamed middle ear mucosa in chronic otitis media

Conclusion: The present study shows that 2–3 weeks after medical treatment the status of middle ear mucosa in draining ears is similar to that of dry ears for at least 3 months.Objective: To measure the time required for an inflamed middle ear mucosa to return into optimal state after appropriate medical treatment in chronic suppurative otitis media (CSOM). To assess optimal timing for elective surgical treatment of draining ears in uncomplicated CSOM.Methods: In this prospective study, the Eustachian tube (ET) mucociliary clearance time (MCT) was used as the method to demonstrate the status of middle ear mucosa. In group 1 (28 patients) ET-MCT was measured in ears that were free of drainage for at least 3 months. In Group 2 (21 patients), ET-MCT was measured in draining ears, who responded to 10–14 days medical treatment, at presentation, after 10 days and 1 month.Results: The ET-MCT was 8.63 ± 1.32 min in group 1 and 28.96 ± 8.19 min in group 2 at presentation; and the difference was statistically significant (p < 0.001). The ET-MCT was 14.76 ± 5.11 min after 10 days and 9.31 ± 2.33 min after 1 month in group 2. The ET-MCT was indifferent between groups 1 and 2 after 1 month (p = 0.235).

Transcanal Endoscopic Antrostomy Hole : Its Utility in Restoring Ventilation Pathway to Epitympanum and Mastoid Antrum During Tympanoplasty

Aim: To evaluate the role of newly created transcanal endoscopic antrostomy hole as a passage in restoring the aeration of epitympanum and mastoid antrum.Materials &amp; Methods: Study design: Retrospective case series study. Study duration: From January 2013 to January 2014. Study place: Private tertiary care hospital. Patients: 27 ears of 23 adult patients (age ranging from 15years to 54years) underwent transcanal endoscopic tympanoplasty for their chronic middle ear diseases in presence of inflamed middle ear mucosa along with radiological shadows of stagnant fluid in their epitympanum and mastoid antrum. Structured three months follow-up was ensured in every case. Intervention: A hole was created at a selected site of posterior meatal wall purely through transcanal endoscopic approach that established direct communication between mastoid antrum and external auditory canal. Thereafter this newly created passage was used for three purposes- assessment of the condition of mastoid antrum, performing the water test for checking epitympanic patency and in few cases placement of temporary tube for postoperative ventilation and drainage of middle ear. Main out come measures: The feasibility, performance and management of transcanal endoscopic antrostomy hole as passage for reestablishing the aeration of epitympanum and mastoid antrum.Results: The chosen site for antrostomy hole was found effective and safe in providing convenient entrance into the mastoid antrum in every case in this study with out facing technical complexity and failure. Postoperative healing of skin over antrostomy hole was found complete in all ears without any inward growth of skin in to mastoid antrum. Available post operative CT scan imaging of temporal bones showed improved aeration in their epitympanum and mastoid antrum.Conclusions: The role of transcanal antrostomy hole has been proved worthy in restoring ventilation pathway to epitympanum and mastoid antrum during tympanoplasty. This antrostomy hole has the potentiality to be considered in future for placement of long term mastoid ventilation tube in order to treat persistent atelectatic middle ear.

HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants

Otitis media with effusion (OME) is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF) mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1α gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006) and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF–mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF–mediated pathways, and we conclude that targeting molecules in HIF–VEGF signaling pathways has therapeutic potential in the treatment of chronic OM.

Two Cases of Middle Ear Adenoma with Neuroendocrine Differentiation (Carcinoid Tumor)

Middle ear adenoma with neuroendocrine differentiation (carcinoid tumor) is a rare benign tumor of the tympanic cavity. Carcinoid tumor is generally derived from primitive stem cells in the gut wall but can be seen in other organs, including the lungs, mediastinum, thymus, liver, pancreas, bronchus, ovaries, prostate, and kidneys. This is unusual considering neuroendocrine cells have not been identified in normal or inflamed middle ear mucosa. Carcinoid tumor of the middle ear represents a class within the spectrum of adenomatous neoplasms. Immunohistochemical techniques have helped clarify that these tumors all share elements of neuroendocrine differentiation. Although histologic and biological similarities with middle ear adenoma exist, carcinoid tumor of the middle ear should be classified as a well-differen tiated neuroendocrine carcinoma because the carcinoid tumor has higher rate of recurrence and incidence of metastasis than middle ear adenoma. Surgical management is the recommended treatment and long-term observation is necessary. � Korean J Otorhinolaryngol-Head Neck Surg 2011;54:573-7 Key WordsZZMiddle ear ㆍCarcinoid tumor.

Emerging applications for OCT in the head and neck

Objectives: To describe the current and promising new applications of Optical Coherence Tomography (OCT) as a helpful tool when imaging the different sites in the head and neck. We used the OCT Niris system, which is the first commercially available OCT device for applications outside the field of ophthalmology. Methods: OCT images were obtained of normal, benign, premalignant and malignant lesions in different areas of the head and neck. The OCT imaging system has a tissue penetration depth of approximately 1-2mm, a scanning range of 2mm and a spatial depth resolution of approximately 10-20μm. Imaging was performed using a flexible probe in two different settings, the outpatient clinic and the operating room. Results: High-resolution cross-sectional images from the larynx were obtained with the patient awake, without the need for general anesthesia, under direct visualization with a flexible fiberoptic endoscope. The OCT probe was inserted through the nasal cavity and placed in slight contact with the laryngeal tissue. In the ears, cholesteatoma was differentiated from inflamed middle ear mucosa by the different hyperintensity. In the neck, normal as well as different pathologies of the thyroid were identified. Conclusions: This system is non invasive and easy to incorporate into the operating room setting as well as the outpatient clinic. It requires minimal set-up and only one person is required to operate the system. OCT has the distinctive capability to obtain highresolution images, and the microanatomy of different sites can be observed. OCT technology has the potential to offer a quick, efficient and reliable imaging method to help the surgeon not only in the operating room but also in the clinical setting to guide surgical biopsies and aid in clinical decision making of different head and neck pathologies, especially those arising form the larynx.

Effect of lipooligosaccharide mutations of Haemophilus influenzae on the middle and inner ears

Objective The purpose of this study was to determine the virulence of nontypeable Haemophilus influenzae 2019 (NTHi 2019) and its two lipooligosaccharide (LOS) mutant strains, B29 (gene htrB) and DK1 (gene rfaD), and compare their effect on the middle ear, round window membrane, and inner ear. Results Fifteen chinchillas were divided into three equal groups and their bullas inoculated bilaterally with 0.5 ml of 10 2 CFU/ml of parent NTHi 2019, B29 or DK1 mutant strains. Two days after inoculation all animals had otitis media and inflamed middle ear mucosa. There was a trend of greater thickness and infiltration of the round window membrane in animals inoculated with the wild-type NTHi strain compared to the mutant strains and a significant increase in both inflammatory cell infiltration and bacteria presence in the scala tympani area of the inner ear. Strial edema was only observed in the wild-type-inoculated group. Conclusions LOS mutants of NTHi appear to have a reduced ability to pass through the round window membrane resulting in less inner ear inflammation and pathological changes.

Cochlear implantation in healthy and otitis-prone children: a prospective study.

To evaluate and compare the timing of surgery, intraoperative findings, and otitis media-related outcome of cochlear implantation in children who are otitis-prone with their counterparts who are not otitis-prone. Prospective. Children referred for cochlear implantation were assigned to a non-otitis-prone group (group A: normal otoscopy on their first visit after referral) or an otitis-prone group (group B: current or a recent history of otitis media at referral). Group B patients were managed using a structured protocol aimed at preimplantation otitis media control. The study reviewed pre-, intra-, and postoperative data. Of the 18 children studied, 8 were assigned to group A (mean age at referral, 40.6 mo) and 10 to group B (mean age at referral, 31.6 mo). For otitis media control, all otitis-prone children underwent ventilating tube insertion (various numbers of procedures before implantation). Only one otitis-prone child required cortical mastoidectomy also. Time from referral to implantation was similar in the two groups (mean, 6.6 mo). High-resolution computed tomography data showed mastoid pneumatization to be significantly smaller in the otitis-prone group, but the facial recess was not smaller in this group. During implantation, 10 children had inflamed middle ear mucosa. Seven of these belonged to group B. All of these seven children had a round window niche obliterated by the inflamed mucosa, which had to be removed for round window membrane identification. After implantation, only one child had drainage through the ventilating tube for more than 1 week. Two children in group B developed otitis media (1 year postimplantation) that was overcome within 1 week. There were no otitis media-related complications. If a structured protocol is used for the control of otitis media before cochlear implantation, otitis media should not require a delay in implantation. In otitis media-prone children, the round window niche is often obscured by inflamed mucosa. Its removal is mandatory for identification of the round window membrane. After cochlear implantation, otitis media is not a frequent occurrence.

Study on adhesion factors in lymphocyte migration to the middle ear mucosa.

We investigated influences of adhesion factors on the migration of antigen-specific IgA-forming cells (ASAFCs) to the middle ear mucosa by means of an in vitro lymphocyte binding assay. Peyer's patch (PP) lymphocytes from guinea pigs with mucosal immunization, which are rich in ASAFCs, more frequently bound with the inflamed middle ear mucosa than those of PP and spleen cells from animals with systemic immunization, in which antigen-specific IgG-forming cells (ASGFCs) were induced (p > .001). The bindings were not affected by antigenic and nonantigenic stimuli to the middle ear mucosa for producing otitis media. On human middle ear mucosa from 10 patients with acute mastoiditis and chronic otitis media, endothelial cells of newly grown vessels were stained strongly with intercellular adhesion molecule (ICAM)-1, and weakly with vascular cell adhesion molecule (VCAM)-1, platelet endothelial cell adhesion molecule (PECAM), and endothelial leukocyte adhesion molecule (ELAM)-1. Many lymphocytes bound mainly to these endothelial cells, and a few cells were observed bound to the basal portion of epithelial cells. The binding of lymphocytes was significantly, but not completely, inhibited by anti-ICAM-1 antibody (p < .001). These findings suggest that PP lymphocytes with activated mucosal immunity more frequently migrate to the inflamed middle ear mucosa, and that those migrations, after extravasation, may be regulated by the interaction between various binding factors and their receptors on lymphocytes, which is different from that of adhesion molecules and their ligands in the extravasation.

Lymphocyte migration to the middle ear mucosa.

We investigated the migration of antigen-specific IgA-forming cells to the middle ear mucosa. Antigen-specific lymphocytes of IgA and IgG classes were induced in guinea pigs according to an immunization strategy previously described. From those animals, chromium 51-labeled lymphocytes of Peyer's patches and spleen were transferred to radiated chimera recipients. The radioactivity levels of the middle ears with antigenic and nonantigenic stimuli were significantly higher than those of the control ears (p < .05). Those levels of radioactivity were influenced neither by origins and subsets of transferred cells nor by antigenic stimuli to the mucosa (p > .05). Many labeled cells were observed in the middle ear effusion, while few were found in the inflamed mucosa. These findings suggest that in the early stage of inflammation, lymphocytes, including antigen-specific T and B cells, may be recruited from the blood circulation to the inflamed middle ear mucosa by nonspecific inflammatory processes that may mask antigen-specific factors in lymphocyte migration.

The histological patterns of normal and inflamed middle ear mucosa

Thirty temporal bones from infants up to the age of 24 months were chosen randomly. Bones were sectioned serially and studied histologically. Inflammatory cellular and mucoid elements were identified and evaluated semiquantitatively. Some inflammatory infiltration was found in all 30 ears. Seven ears from infants up to 1 month of age presented inflammatory infiltration only. Twenty-three ears presented both cellular and mucoid elements. All temporal bones exhibiting mucoid elements showed concomitant cellular inflammatory infiltration. Practically no temporal bones in this age group were free of inflammatory elements, with secretory features appearing chronologically after the cellular ones.

Assessment of Middle-Ear Status During Experimental Otitis Media Using Magnetic Resonance Imaging

Magnetic resonance imaging has proved to be a useful tool for in vivo imaging of a variety of tissues. In this study, magnetic resonance imaging was applied to the middle ear of experimental animals with otitis media. Results showed that the presence and distribution of effusion within the middle-ear space could be readily determined. Moreover, following injection of gadolinium-diethylenetriaminepentaacetic acid, a contrast agent, the inflamed middle-ear mucosa could be resolved. A comparison between magnetic resonance imaging and tympanometry with respect to the diagnosis of effusion showed that negative pressure tympanograms were equivocal (50% effusion) and that flat or normal tympanograms were in error in approximately 20% of the observations. These data document a role for magnetic resonance imaging in in vivo studies of the pathogenesis of otitis media with effusion.

Induction of antigen-specific IgA-forming cells in the middle ear mucosa.

Antigen-specific IgA-forming cells were induced in the middle ear mucosa by the use of soluble and particulate forms of dinitrophenylated ovalbumin. Hartley guinea pigs were locally immunized in the duodenum (group A) and trachea (group B) with the particulate form of dinitrophenylated ovalbumin one week after systemic priming with the soluble form. Otitis media was then induced with the intratympanic inoculation of the antigen. The control animals (group C) received only intratympanic inoculation after systemic priming. The mean titers of salivary IgA antibody of groups A and B were significantly greater than that of group C, and the mean value of serum IgG antibody titers of group C was significantly greater than those of groups A and B. The occurrences of otitis media in groups A and B were significantly suppressed, and histologic changes of the middle ear mucosa of groups A and B were slighter than those of group C. Antigen-specific IgA-forming cells were detected in the inflamed middle ear mucosa from group A and B animals, while these cells could not be found in group C animals. These results demonstrate the immunization strategy whereby the mucosal IgA immunity of the middle ear cavity can be effectively induced and enhanced to prevent otitis media.

Inflammatory Changes Reflected in Middle Ear Effusion in Otitis Media

Otitis media (OM) is an extremely wide-spread disease, and the presence of middle ear effusion (MEE) is a common phenomena in OM. The analyses of MEE provide important information for better understanding of etiology and evaluation of inflammatory stages of the middle ear cavity. Well investigated etiologic factors of OM have included negative pressures within the middle ear cavity secondary to Eustachian tube dysfunction, and bacterial or viral infection. It is quite conceivable that the biochemical, cytological and immunochemical products found in the middle ear mucosa (MEM) and MEE during OM may contribute to the clinical course of the disease. The sources of these inflammatory components include: inflamed epithelial cells of MEM, cells of the subepithelial space, vasogenic origins, bacterial and/or inflammatory cell products in MEE. In animal studies (serous otitis media [SOM] and purulent otitis media [POM]), interesting correlations between sequential biochemical and cytological findings have been observed. The vasodilation, increased blood vessel permeability, and the release of intracellular products both from inflamed middle ear mucosa and inflammatory cells are determining factors for the biochemical changes of MEE. Recently, the importance of the role of the subepithelial space (SES) in the pathogenesis of various types of OM has been emphasized in human studies. A strong cellular-immune response with proliferation of fibroblasts, collagen fibers, plasma cells, lymphocytes, macrophages, along with an increase in capillary networks have been characterized with SES changes in OM. Analysis of MEE by biochemical and immunochemical markers (prostaglandins, immunoglobulins, intracellular enzymes) have reflected inflammatory changes in the MEM of various types and stages of OM.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of antileukoprotease in middle ear mucosa.

The localization of antileukoprotease was studied immunohistologically in normal middle ear mucosa specimens obtained at autopsy and in chronically inflamed middle ear mucosa specimens obtained at middle ear surgery for chronic otitis media. In the sections of normal as well as in the sections of chronically inflamed middle ear mucosa, antileukoprotease localization was confined to PAS-positive goblet cells of surface epithelium and to PAS-positive goblet-like cells of submucosal glands and crypts, whereas ciliated mucosal cells and stratified squamous epithelial cells were devoid of anti-leukoprotease. In comparison with normal middle ear mucosa, an increased number of goblet cells--and thus an increased number of cells containing antileukoprotease--was present in the chronically inflamed middle ear mucosa. Since antileukoprotease is a potent inhibitor of granulocyte elastase and Cathepsin G, it was concluded that this proliferation of the respiratory epithelium during inflammatory processes in the middle ear indicates an increased activity of the biologic defence system against the action of granulocyte proteases.

Secretory properties of chronically inflamed middle ear mucosa.

Based on systematic examination of 13 chronically infected temporal bones, serially sectioned and stained for mucus, the following conclusions concerning mucosal secretory properties were drawn: (1) Chronically inflamed middle ear mucosa showed increased secretory capacity in the form of goblet and other secretory cells. Great numbers of secreting cells were seen, especially in the areas of taller epithelium; in places mucus-positivity could be demonstrated even in the ciliated cells. In certain areas the respiratory epithelium could even be replaced by mucous epithelium. Increased secretory function was felt to be due partly to secretory metaplasia, partly to secretory proliferation. (2) Glands or gland-like structures were always present, but in half the cases only their degenerative forms were left. The number and activity of the glands depended upon the stage of the chronic process. When the situation had become chronic with hyperplastic mucosa the secretory elements increased; when the mucosa had bec...