scholarly journals Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants

2020 ◽  
pp. jmedgenet-2020-106844 ◽  
Author(s):  
Daniel N. Frank ◽  
Arnaud P. J. Giese ◽  
Lena Hafren ◽  
Tori C. Bootpetch ◽  
Talitha Karisse L. Yarza ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Head And Neck ◽  
Otitis Media ◽  
Middle Ear ◽  
Rare Variants ◽  
Missense Variant ◽  
Middle Ear Mucosa ◽  
Significant Heritability ◽  
Epithelial Barriers ◽  
And Shifts

BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma.ConclusionSPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

Effects of Platelet Activating Factor on the Tubotympanic Mucosa and Inner Ear in the Guinea Pig

1998 ◽  
Vol 107 (10) ◽  
pp. 876-884 ◽  
Author(s):  
Yoshiharu Ohno ◽  
Yoshihiro Ohashi ◽  
Hideki Okamoto ◽  
Yoshikazu Sugiura ◽  
Yoshiaki Nakai
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Otitis Media ◽  
Middle Ear ◽  
Otitis Media With Effusion ◽  
Platelet Activating Factor ◽  
Sensorineural Hearing ◽  
Ciliary Activity ◽  
Middle Ear Mucosa

The effect of platelet activating factor (PAF) was studied to elucidate its role in the pathogenesis of otitis media and sensorineural hearing loss. The PAF alone did not induce a reduction of ciliary activity of the cultured middle ear mucosa. However, a dose-dependent decrease in ciliary activity was observed in the presence of the medium containing both PAF and macrophages. Intravenous injection of PAF did not induce dysfunction of the mucociliary system or morphologic changes of epithelium in the tubotympanum, but cytoplasmic vacuolization and ballooning were observed in the inner ear within 1 hour after injection of PAF. In contrast, intratympanic injection of PAF induced mucociliary dysfunction and some pathologic changes in the tubotympanum. Intratympanic inoculation of PAF induced no pathologic findings in the inner ear. These results suggest that PAF is at least partially involved in the pathogenesis of certain middle ear diseases such as otitis media with effusion. Additionally, PAF might be involved in the pathogenesis of some types of unexplained sensorineural hearing loss.

Acute Suppurative Otitis Media

PEDIATRICS ◽  
1975 ◽  
Vol 56 (2) ◽  
pp. 285-294
Author(s):  
D. Stewart Rowe
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Pathogenic Bacteria ◽  
Acute Otitis Media ◽  
Polymorphonuclear Cells ◽  
Secretory Otitis Media ◽  
Middle Ear Mucosa ◽  
Suppurative Otitis Media ◽  
Middle Ear Fluid ◽  
Purulent Fluid

Most pediatricians recognize and treat acute otitis media several times each day. Yet there is wide disagreement about certain aspects of its diagnosis and treatment, despite a large and growing literature on the subject. This review attempts to summarize what is known about acute otitis media in children. DEFINITION Acute suppurative otitis media is distinguished from secretory (serous) otitis media by the presence of purulent fluid in the middle ear. Pathogenic bacteria may be cultured from the majority of needle aspirates of this purulent fluid. In secretory otitis media, relatively few polymorphonuclear cells are present in the middle ear fluid, which is either thin and straw-colored (serous) or thick and translucent grey (mucoid). The fluid has the chemical characteristics either of a transudate of plasma or of a mucoid secretion, presumably produced by goblet cells and mucous glands which are greatly increased in the middle ear mucosa of patients with secretory otitis media. Cultures of this middle ear fluid are usually negative for pathogenic bacteria and viruses. Suppurative otitis media can be diagnosed positively only by aspiration of purulent fluid from the middle ear, but this procedure is rarely necessary for initial diagnosis and management. Clinical findings helpful in distinguishing suppurative from secretory otitis media are discussed below. INCIDENCE In a study of 847 British children during the first five years of life, 19% had at least one episode of otitis media; one third of these had more than one episode. This was considered to be a minimal estimate in these children, since otorrhea was the chief criterion for diagnosis.

The Immune Imbalance of Treg/Th17 in Otitis Media of Effusion Patients May Be Related to PI3K/Akt/mTOR Signaling Activation in the Middle Ear Mucosa

2020 ◽  
Author(s):  
Zhiyuan Tang ◽  
Xianhai Zeng ◽  
Juanjuan Li ◽  
Hua Zhang ◽  
Hancheng Wu ◽  
...  
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Rat Model ◽  
Mtor Signaling ◽  
Secretory Otitis Media ◽  
Middle Ear Mucosa ◽  
Foxp3 Mrna ◽  
Abnormal Immune Response ◽  
Signaling Activation ◽  
Immune Imbalance

Abstract Objective: To assess whether secretory otitis media may be caused by immune imbalance of Treg/Th17 mediated by PI3K/Akt/mTOR signaling, so as to find new therapeutic target.Methods: IL-17, TGF- and IL-6, IL-10 and Th17 cytokines were detected in peripheral blood of OME patients (PC group) and healthy people (NC group) by ELISA. The expression of ROR t mRNA and Foxp3mRNA in PBMC was detected by RT-PCR. OME rat model was established and the changes of lymphocytes in middle ear mucosa and spleen and PI3K/Akt/mTOR signaling in middle ear mucosa were detected by HE staining, IHC, WB and flow cytometry.Results: The immune imbalance of Treg/Th17 in secretory otitis media (OME) was confirmed by the expression of cytokines in OME serum and analysis of ROR T and Foxp3 mRNA which was Th17 and Treg specific transcription respectively. OME rat model further confirmed that Treg/Th17 imbalance could lead to OME as demonstrated by staining of MIDDLE ear mucosa and expression of ROR T and Foxp3. PI3K, Akt, and mTOR proteins were expressed in the MIDDLE ear mucosa of OME group and CON group, respectively. Compared with CON group, the expression of P-MTOR and P-PI3K proteins in the middle ear mucosa of OME group was significantly increased.Conclusions: Treg/Th17 imbalances are found in OME patients and OME animal model and the pathogenic mechanism may be due to systemic abnormal immune response, activated PI3K/Akt/mTOR signaling, abnormal T cell differentiation, leading to middle ear mucosal hyperemia, edema and subsequent occurrence of OME.

S224 – Efficacy of Long Silastic Sheet in COM Surgery

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P150-P150
Author(s):  
Hyong-Ho Cho ◽  
Hyun-Seok Choi ◽  
Chul-Ho Jang ◽  
Yong-Bum Cho
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Valsalva Maneuver ◽  
Chronic Otitis Media ◽  
Mastoid Cavity ◽  
Middle Ear Mucosa ◽  
Hearing Result ◽  
Staged Operation ◽  
Canal Wall Up

Objectives To determine the effect of long silastic sheet for middle ear aeration in chronic otitis media surgery. Methods Between January 2003 and May 2007, 46 patients underwent planned staged canal wall up tympanomastoidetomy, because possibility of residual cholesteatoma and severe swelling middle ear mucosa, especially around the stapes. Long silastic sheet was inserted from mastoid cavity to middle ear via facial recess during operation procedure. To determine the effect of long silastic sheet for recovery of mastoid aeration, various factors such as computed tomography grading, Valsalva maneuver grading for Eustachian function, and hearing result were compared. Results During the average follow-up of 31 months, there was 1 recurred chronic otitis media which was revealed tuberculosis otitis media. Intact tympanic membrane was obtained in 45(97.8%) of 46 patients. In CT grading, middle ear aeration was increased significantly (p<0.05). Air-Bone gap was significantly decreased after staged operation, preoperative average ABG was 29.7dB and last average ABG was 21.0dB (p <0.05). But Eustachian function using Valsalva manerver was not significantly changed (p >0.05). Conclusions Long silastic sheet insertion from mastoid to middle ear is statistically effective for amelioration of middle ear and mastoid aeration after the first-stage operation.

scholarly journals Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media

JAMA ◽  
2006 ◽  
Vol 296 (2) ◽  
pp. 202 ◽  
Author(s):  
Luanne Hall-Stoodley ◽  
Fen Ze Hu ◽  
Armin Gieseke ◽  
Laura Nistico ◽  
Duc Nguyen ◽  
...  
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Direct Detection ◽  
Chronic Otitis Media ◽  
Bacterial Biofilms ◽  
Middle Ear Mucosa

Experimental Otitis Media Evaluated by Magnetic Resonance Imaging: An in Vivo Model

1992 ◽  
Vol 101 (3) ◽  
pp. 248-254 ◽  
Author(s):  
Kenny H. Chan ◽  
William J. Doyle ◽  
J. Douglas Swarts ◽  
David Kardatzke ◽  
Yoshie Hashida ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Otitis Media ◽  
Middle Ear ◽  
Washout Rate ◽  
In Vivo Model ◽  
Resonance Imaging ◽  
Middle Ear Mucosa

The use of magnetic resonance imaging in otitis media research is being explored in our laboratory. In this study, we present a new method for studying changes in the middle ear cleft due to an episode of induced otitis media in the chinchilla model. It uses gadolinium-diethylenetriamine pentaacetic acid, a magnetic resonance imaging contrast agent, to examine the uptake and washout characteristics of middle ear mucosa during an inflammatory episode. Parameters such as the time to maximum intensity of the mucosa and the washout rate of the contrast agent from the mucosa were significantly correlated to the duration of the infection.

scholarly journals High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 224 ◽  
Author(s):  
Nicola Malagutti ◽  
John Charles Rotondo ◽  
Luca Cerritelli ◽  
Claudio Melchiorri ◽  
Monica De Mattei ◽  
...  
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Dna Sequences ◽  
Direct Sequencing ◽  
Chronic Otitis Media ◽  
Human Papillomaviruses ◽  
Middle Ear Mucosa ◽  
Suppurative Otitis Media ◽  
Ear Diseases ◽  
Hpv Dna

Background. Previous studies reported human papillomaviruses (HPVs) in middle ear tumors, whereas these viruses have been poorly investigated in chronic inflammatory middle ear diseases. We investigated HPVs in non-tumor middle ear diseases, including chronic otitis media (COM). Methods. COM specimens (n = 52), including chronic suppurative otitis media (CSOM) (n =38) and cholesteatoma (COMC) (n = 14), as well as normal middle ear (NME) specimens (n = 56) were analyzed. HPV sequences and DNA loads were analyzed by quantitative-PCR. HPV genotyping was performed by direct sequencing. Results. HPV DNA was detected in 23% (12/52) of COM and in 30.4% (17/56) of NME (p > 0.05). Specifically, HPV DNA sequences were found in 26.3% (10/38) of CSOM and in 14.3% (2/14) of COMC (p > 0.05). Interestingly, the HPV DNA load was higher in COMC (mean 7.47 copy/cell) than in CSOM (mean 1.02 copy/cell) and NME (mean 1.18 copy/cell) (P = 0.03 and P = 0.017 versus CSOM and NME, respectively). HPV16 and HPV18 were the main genotypes detected in COMC, CSOM and NME. Conclusions. These data suggest that HPV may infect the middle ear mucosa, whereas HPV-positive COMCs are associated with higher viral DNA loads as compared to NME.

Effect of Prostaglandin on the Composition of Chinchilla Middle Ear Effusion

1980 ◽  
Vol 89 (3_suppl) ◽  
pp. 153-160 ◽  
Author(s):  
Timothy T. K. Jung ◽  
S. K. Juhn ◽  
Douglas M. Smith ◽  
Jonathan M. Gerrard
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Resorption ◽  
Otitis Media ◽  
Middle Ear ◽  
Time Course ◽  
Unsaturated Fatty Acids ◽  
Biological Activities ◽  
Middle Ear Mucosa ◽  
Acid And Alkaline Phosphatase ◽  
Wide Range

Prostaglandins (PGs) are naturally occurring, cyclic, unsaturated fatty acids which possess a wide range of potent biological activities. PGs have been found in human middle ear effusions and might have implications for understanding the inflammation and possibly the bone resorption seen in chronic otitis media. We have measured PGs by radioimmunoassay in middle ear effusions (MEE) from experimentally induced serous otitis media (SOM) and purulent otitis media (POM) in chinchillas. PGE2 levels were significantly higher in the POM group compared to the SOM group. We have also demonstrated that chinchilla middle ear mucosa can convert arachidonic acid (AA), a precursor of PGs, to PG by injecting 14C-AA into bullae and assaying using radiochromatography. This conversion was completely blocked by both indomethacin and aspirin given orally or by direct injection into the middle ear. We then injected 50 μg of PGE2 into chinchilla bullae to assess its effect on the composition of MEE. First, the time course of PGE2 metabolism after its injection into the middle ear (ME) was determined by thin-layer chromatography (TLC) of labelled and unlabelled PGE2. Following this, serial daily injections of PGE2 and normal saline as control were made for one, three, and seven days. MEE and serum were collected and assayed for lactate dehydrogenase (LDH), acid and alkaline phosphatase, calcium, protein and hexosamine. Compared to the control, the levels of LDH, acid and alkaline phosphatase, calcium and protein were significantly elevated. Hexosamine levels were higher than the control at one and three days but did not differ significantly at seven days from the control. We have therefore demonstrated that chinchilla middle ear mucosa has the ability to synthesize PG from AA and suggest an active role for PGs in the inflammation and in the bone resorption seen in otitis media.

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