Panel 3: Genetics and Precision Medicine of Otitis Media

Lin, Jizhen; Hafrén, Lena; Kerschner, Joseph E.; Li, Jian Dong; Brown, Steve; Zheng, Qing Yin; Preciado, Diego; Nakamura, Yoshihisa; Huang, Qiuyuan; Zhang, Yan

doi:10.1177/0194599816685559

Cited by 5 publications

(6 citation statements)

References 89 publications

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“…This suggests that host genetics may play a role in engendering intra‐species diversification and genotypic variation regarding immunologic response. Identification of genetic loci that are associated with OM is an avenue of precision medicine which is currently under study and has shed light into potential disease mechanisms and novel therapeutic strategies for certain at‐risk groups (Bhutta et al, 2017; Geng et al, 2019; Lin et al, 2017).…”

Section: Clinical Relevance Of Nasopharyngeal Morphology In Humansmentioning

confidence: 99%

Clinical perspectives on nasopharyngeal morphology in humans

Rohde

Friedland

2022

The Anatomical Record

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The nasopharynx is an integral component of the upper aerodigestive tract, whose morphologic features share an intimate relationship with a vast array of clinical, functional, and quality of life conditions related to contemporary humans. Its composite architecture and central location amidst the nasal cavity, pharyngotympanic tube, palate, and skull base bears implications for basic physiologic functions including breathing, vocalization, and alimentation. Over the course of evolution, morphological modifications of nasopharyngeal anatomy have occurred in genus Homo which serve to distinguish the human upper aerodigestive tract from that of other mammals. Understanding of these adaptive changes from both a comparative anatomy and clinical perspective offers insight into the unique blueprint which underpins many clinical pathologies currently encountered by anthropologists, scientists, and otorhinolaryngologists alike. This discussion intends to familiarize readers with the fundamental role that nasopharyngeal morphology plays in upper aerodigestive tract conditions, with consideration of its newfound clinical relevance in the era of the COVID‐19 pandemic.

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Section: Clinical Relevance Of Nasopharyngeal Morphology In Humansmentioning

confidence: 99%

Clinical perspectives on nasopharyngeal morphology in humans

Rohde

Friedland

2022

The Anatomical Record

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“…Thus, differences in host PRR expression and subsequent signalling pathway activation can lead to differences in how the innate immune response is regulated and how OM disease progresses. There is growing evidence that host genetic polymorphisms in PRR genes and differences in PRR expression can dysregulate innate immune signalling pathways in response to otopathogens and therefore play a significant role in the induction and pathogenesis of OM (Lin et al, 2017). Furthermore, NTHi is recently reported to utilise phase variable epigenetic regulation to modify and adapt its phenotype but also modify host immune responses (Robledo-Avila et al, 2020), creating a shifting immunological target for the host (Parrish et al, 2019).…”

Section: Pathogen Recognition and Activation Of Signalling Pathways Within The Innate Immune Responsementioning

confidence: 99%

“…Allelic association studies have identified polymorphisms related to the development of OM in genes encoding TLR4 receptors, IL-6, IL-10 and TNF-a (Emonts et al, 2007), mannose-binding lectins (Wiertsema et al, 2006), surfactant (Ramet et al, 2001), and Mucin gene MUC5AC (Ubell et al, 2010) [for review see (Mittal et al, 2014a;Lin et al, 2017;Geng et al, 2019)]. TLR4 locus polymorphisms have also been examined in patients with RAOM or COME and demonstrated a role for TLR4 in the regulation of the innate immune response.…”

Section: Host Factors That Modulate the Mucosal Response In Ommentioning

confidence: 99%

Innate Immunity in the Middle Ear Mucosa

Massa

Spann

Cripps

2021

Front. Cell. Infect. Microbiol.

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Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

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“…Many OM mouse models are characterized by gene mutations that cause defects in craniofacial anatomy or ME cellular function, including mucin production, ciliated cell function, ET structure and function, ME cavitation, and mucosal hyperplasia. Many of these mouse mutants spontaneously develop COME and thus can serve as good models for studying COME (Bhutta et al, 2017b;Lin et al, 2017).…”

Section: Genes Involved In Anti-inflammatory Responses In Ommentioning

confidence: 99%

“…Genetics has also been shown to play a critical role in host susceptibility to OM; therefore, identifying genetic loci that are associated with OM could help to elucidate potential disease mechanisms and develop effective therapies. Many host genes identified and associated with OM have been reviewed before (Rye et al, 2011a;Kurabi et al, 2016;Bhutta et al, 2017b;Lin et al, 2017). In this review, we provide an update on the identification of new host genes, make progress in our understanding of previously identified genes in OM predisposition, and discuss the prospects for future research in this field.…”

Section: Introductionmentioning

confidence: 99%

Current Understanding of Host Genetics of Otitis Media

Geng¹,

Wang²,

Chen³

et al. 2020

Front. Genet.

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The pathogenesis of otitis media (OM), an inflammatory disease of the middle ear (ME), involves interplay between many different factors, including the pathogenicity of infectious pathogens, host immunological status, environmental factors, and genetic predisposition, which is known to be a key determinant of OM susceptibility. Animal models and human genetics studies have identified many genes and gene variants associated with OM susceptibility: genes that encode components of multiple signaling pathways involved in host immunity and inflammatory responses of the ME mucosa; genes involved in cellular function, such as mucociliary transport, mucin production, and mucous cell metaplasia; and genes that are essential for Eustachian tube (ET) development, ME cavitation, and homeostasis. Since our last review, several new mouse models with mutations in genes such as CCL3, IL-17A, and Nisch have been reported. Moreover, genetic variants and polymorphisms in several genes, including FNDC1, FUT2, A2ML1, TGIF1, CD44, and IL1-RA variable number tandem repeat (VNTR) allele 2, have been identified as being significantly associated with OM. In this review, we focus on the current understanding of the role of host genetics in OM, including recent discoveries and future research prospects. Further studies on the genes identified thus far and the discovery of new genes using advanced technologies such as gene editing, next generation sequencing, and genome-wide association studies, will advance our understanding of the molecular mechanism underlying the pathogenesis of OM and provide new avenues for early screening and developing effective preventative and therapeutic strategies to treat OM.

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Panel 3: Genetics and Precision Medicine of Otitis Media

Cited by 5 publications

References 89 publications

Clinical perspectives on nasopharyngeal morphology in humans

Clinical perspectives on nasopharyngeal morphology in humans

Innate Immunity in the Middle Ear Mucosa

Current Understanding of Host Genetics of Otitis Media

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