Materiały źródłowe

• #1 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Acute otitis media is defined as an infection of the middle ear space. […] Infection of the middle ear can be viral, bacterial, or coinfection. The most common bacterial organisms causing otitis media are Streptococcus pneumoniae, followed by non-typeable Haemophilus influenzae(NTHi) and Moraxella catarrhalis. […] Otitis media begins as an inflammatory process following a viral upper respiratory tract infection involving the mucosa of the nose, nasopharynx, middle ear mucosa, and Eustachian tubes. Due to the constricted anatomical space of the middle ear, the edema caused by the inflammatory process obstructs the narrowest part of the Eustachian tube leading to a decrease in ventilation. This leads to a cascade of events resulting in an increase in negative pressure in the middle ear, increasing exudate from the inflamed mucosa, and buildup of mucosal secretions, which allows for the colonization of bacterial and viral organisms in the middle ear. The growth of these microbes in the middle ear then leads to suppuration and, eventually, frank purulence in the middle ear space.

• #2 Otitis Media: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/994656-overview

  Otitis media (OM) is any inflammation of the middle ear, without reference to etiology or pathogenesis. It can be classified into many variants on the basis of etiology, duration, symptomatology, and physical findings. […] The most important factor in middle ear disease is eustachian tube (ET) dysfunction (ETD), in which the mucosa at the pharyngeal end of the ET is part of the mucociliary system of the middle ear. Interference with this mucosa by edema, tumor, or negative intratympanic pressure facilitates direct extension of infectious processes from the nasopharynx to the middle ear, causing OM. […] In children, developmental alterations of the ET, an immature immune system, and frequent infections of the upper respiratory mucosa all play major roles in AOM development. Studies have demonstrated how viral infection of the upper respiratory epithelium leads to increased ETD and increased bacterial colonization and adherence in the nasopharynx.

• #3 Ear infection (middle ear) – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/ear-infections/symptoms-causes/syc-20351616

  An ear infection, also known as acute otitis media, is an infection of the air-filled space behind the eardrum, known as the middle ear. […] A bacterium or virus in the middle ear causes an ear infection. This infection often comes from another illness, such as a cold, flu or allergy. These can cause the inside the nose, throat and ears to be swollen and stuffy. […] In an ear infection, narrow tubes that run from the middle ear to high in the back of the throat, also known as eustachian tubes, can become swollen and blocked. This can lead to mucus buildup in the middle ear. This mucus can become infected and cause ear infection symptoms. […] Swollen eustachian tubes can become blocked, causing fluids to build up in the middle ear. This fluid can become infected and cause the symptoms of an ear infection. […] Adenoids are near the opening of the eustachian tubes. Swelling of the adenoids can block the tubes. This can lead to middle ear infection, especially in children.

• #4 Acute otitis media in adults – UpToDate

  https://www.uptodate.com/contents/acute-otitis-media-in-adults/print

  Acute otitis media (AOM) is an acute, suppurative infectious process marked by the presence of infected middle ear fluid and inflammation of the mucosa lining the middle ear space. The infection is most frequently precipitated by impaired function of the Eustachian tube, resulting in the retention and suppuration of retained secretions. […] Eustachian tube dysfunction is the most important factor in the pathogenesis of middle ear infections in both childhood and adulthood. Eustachian tube dysfunction induces a relative negative pressure in the middle ear space, with the lack of aeration and accumulation of fluid providing an environment conducive to the development of AOM or otitis media with effusion.

• #5 Acute otitis media in adults – UpToDate

  https://www.uptodate.com/contents/acute-otitis-media-in-adults-suppurative-and-serous

  Eustachian tube dysfunction, commonly related to seasonal allergic rhinitis or upper respiratory tract infection, is the most important factor in the pathogenesis of middle ear infections in adults. […] Eustachian tube dysfunction is the most important factor in the pathogenesis of middle ear infections in both childhood and adulthood. Eustachian tube dysfunction induces a relative negative pressure in the middle ear space, with the lack of aeration and accumulation of fluid providing an environment conducive to the development of AOM or otitis media with effusion. […] The infection is most frequently precipitated by impaired function of the Eustachian tube, resulting in the retention and suppuration of retained secretions.

• #6 Acute Otitis Media: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/859316-overview

  Obstruction of the eustachian tube appears to be the most important antecedent event associated with AOM. The vast majority of AOM episodes are triggered by an upper respiratory tract infection (URTI) involving the nasopharynx. […] The infection is usually of viral origin, but allergic and other inflammatory conditions involving the eustachian tube may create a similar outcome. Inflammation in the nasopharynx extends to the medial end of the eustachian tube, creating stasis and inflammation, which, in turn, alter the pressure within the middle ear. These changes may be either negative (most common) or positive, relative to ambient pressure. […] Stasis also permits pathogenic bacteria to colonize the normally sterile middle ear space through direct extension from the nasopharynx by reflux, aspiration, or active insufflation.

• #7 Otitis media – Wikipedia

  https://en.wikipedia.org/wiki/Otitis_media

  The common cause of all forms of otitis media is dysfunction of the Eustachian tube. This is usually due to inflammation of the mucous membranes in the nasopharynx, which can be caused by a viral upper respiratory tract infection (URTI), strep throat, or possibly by allergies. […] By reflux or aspiration of unwanted secretions from the nasopharynx into the normally sterile middle-ear space, the fluid may then become infected usually with bacteria. The virus that caused the initial upper respiratory infection can itself be identified as the pathogen causing the infection.

• #8 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Several risk factors can predispose children to develop acute otitis media. The most common risk factor is a preceding upper respiratory tract infection. Other risk factors include male gender, adenoid hypertrophy (obstructing), allergy, daycare attendance, environmental smoke exposure, pacifier use, immunodeficiency, gastroesophageal reflux, parental history of recurrent childhood OM, and other genetic predispositions. […] In serous acute otitis media (SAOM), inflammation of the middle ear and the eustachian tube has been identified as the major precipitating factor. Venous or lymphatic stasis in the nasopharynx or the eustachian tube plays a vital role in the pathogenesis of AOM. Inflammatory cytokines attract plasma cells, leukocytes, and macrophages to the site of inflammation.

• #9

  https://bpac.org.nz/2022/otitis-media.aspx

  Otitis media is defined as inflammation of the middle ear and is classified into three categories: Acute otitis media (AOM; most common): acute inflammation and effusion of the middle ear, with rapid onset of symptoms and signs consistent with an ear infection; in younger children, symptoms may be non-specific […] Otitis media is characterised by middle ear and tympanic membrane inflammation resulting from an upper respiratory tract infection due to viral (e.g. respiratory syncytial virus, rhinovirus, influenza viruses, adenovirus) or bacterial infection (e.g. Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis), or a combination of both. […] Factors influencing the risk of a child developing otitis media are divided into individual or environmental and may be modifiable or non-modifiable.

• #10 Acute Otitis Media: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/859316-overview

  Obstruction of the eustachian tube appears to be the most important antecedent event associated with AOM. The vast majority of AOM episodes are triggered by an upper respiratory tract infection (URTI) involving the nasopharynx. […] The infection is usually of viral origin, but allergic and other inflammatory conditions involving the eustachian tube may create a similar outcome. Inflammation in the nasopharynx extends to the medial end of the eustachian tube, creating stasis and inflammation, which, in turn, alter the pressure within the middle ear. These changes may be either negative (most common) or positive, relative to ambient pressure. […] Stasis also permits pathogenic bacteria to colonize the normally sterile middle ear space through direct extension from the nasopharynx by reflux, aspiration, or active insufflation.

• #11 Otitis Media: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/1001/p435.html/1000

  Acute otitis media is usually a complication of eustachian tube dysfunction that occurs during a viral upper respiratory tract infection. […] Bacteria can be isolated from middle ear fluid cultures in 50% to 90% of cases of AOM and OME. […] Risk factors for AOM are listed in Table 1. […] An AOM diagnosis requires moderate to severe bulging of the tympanic membrane, new onset of otorrhea not caused by otitis externa, or mild bulging of the tympanic membrane associated with recent onset of ear pain (less than 48 hours) or erythema. […] OME is defined as middle ear effusion in the absence of acute symptoms. […] Inflammation with bulging of the tympanic membrane on otoscopy is highly predictive of AOM. […] Antibiotic therapy for AOM is often associated with diarrhea. […] Children with persistent, significant AOM symptoms despite at least 48 to 72 hours of antibiotic therapy should be reexamined.

• #12 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Acute otitis media is defined as an infection of the middle ear space. […] Infection of the middle ear can be viral, bacterial, or coinfection. The most common bacterial organisms causing otitis media are Streptococcus pneumoniae, followed by non-typeable Haemophilus influenzae(NTHi) and Moraxella catarrhalis. […] Otitis media begins as an inflammatory process following a viral upper respiratory tract infection involving the mucosa of the nose, nasopharynx, middle ear mucosa, and Eustachian tubes. Due to the constricted anatomical space of the middle ear, the edema caused by the inflammatory process obstructs the narrowest part of the Eustachian tube leading to a decrease in ventilation. This leads to a cascade of events resulting in an increase in negative pressure in the middle ear, increasing exudate from the inflamed mucosa, and buildup of mucosal secretions, which allows for the colonization of bacterial and viral organisms in the middle ear. The growth of these microbes in the middle ear then leads to suppuration and, eventually, frank purulence in the middle ear space.

• #13 Otitis Media (Middle Ear Infections) | ENT & Allergy of Delaware

  https://entad.org/resources/patient-information-dr-teixido/otitis-media-middle-ear-infections/

  Otitis media is an infection of the air space behind the eardrum, which we call the middle ear. […] Middle ear infections (otitis media) generally occur because of improper function of the Eustachian tube. […] Eustachian tube dysfunction: The most common reason for Eustachian tube problems is swelling of the lining of the Eustachian tube, which causes it to remain closed, even though the muscles of the throat are attempting to open it while swallowing. […] If air cannot get in through the Eustachian tube to replace the nitrogen which has been absorbed, then the pressure in the middle ear space will continue to fall. […] The pressure pulls inward on the eardrum and on the first hearing bone (the malleus), causing the chain of hearing bones to become stiff and the hearing muffled. […] If the negative pressure gets great enough and stays for long enough, it will actually suck blood out of the capillaries in the lining of the middle ear.

• #14 Otitis Media (Acute) – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/middle-ear-and-tympanic-membrane-disorders/otitis-media-acute

  Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. […] The etiology of acute otitis media may be viral or bacterial. […] In neonates, gram-negative enteric bacilli, particularly Escherichia coli, and Staphylococcus aureus cause acute otitis media. […] In older infants and children 14 years, the most common organisms are Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and nontypeable Haemophilus influenzae; less common causes are group A beta-hemolytic streptococci and S. aureus. […] In patients 14 years, S. pneumoniae, group A beta-hemolytic streptococci, and S. aureus are most common, followed by H. influenzae. […] Complications of acute otitis media are uncommon. In rare cases, bacterial middle ear infection spreads locally, resulting in acute mastoiditis, petrositis, or labyrinthitis.

• #15 Otitis Media With Effusion: Comparative Effectiveness of Treatments | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/ear-infection/research-protocol

  Otitis media with effusion (OME) is defined as a collection of fluid in the middle ear without signs or symptoms of ear infection. It typically arises when the Eustachian tubes are not functioning normally. When this happens, pressure changes occur in the middle ear and fluid can accumulate. […] OME can be associated with discomfort and a feeling of fullness in the ear. Patients with OME are also prone to episodes of acute otitis media (AOM). Temporary hearing loss is common among OME patients. This hearing loss is often mild (i.e., worsened or with hearing threshold elevated by about 10 dB), but in some cases moderate or severe hearing loss can occur. […] Diagnostically, OME must be first identified and then distinguished from AOM. OME is diagnosed with the presence of fluid behind the tympanic membrane, without acute onset or signs of inflammation or infection. AOM on the other hand, while it may include Eustachian tube dysfunction and middle ear fluid, it must include signs of acute inflammation or infection.

• #16 Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7062565/

  To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. […] The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. […] Viral infection is required for the initial development of bacterial AOM. Recent studies have shown that the presence of respiratory viruses in the nasopharynx is not enough for the development of AOM; viral replication and the respiratory symptoms caused by the viral infection are also necessary.

• #17 Otitis Media: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/994656-overview

  Certain viral infections cause abnormal host immune and inflammatory responses in the ET mucosa and subsequent microbial invasion of the middle ear. The host immune and inflammatory response to bacterial invasion of the middle ear produces fluid in the middle ear and the signs and symptoms of AOM. […] Although interactions between the common pathogenic bacteria in AOM and certain viruses are not fully understood, strong evidence indicates that these interactions often lead to more severe disease, lowered response to antimicrobial therapy, and OME development following AOM.

• #18 Acute Otitis Media: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/859316-overview

  The response is the establishment of an acute inflammatory reaction characterized by typical vasodilatation, exudation, leukocyte invasion, phagocytosis, and local immunologic responses within the middle ear cleft, which yields the clinical pattern of AOM. […] To become pathogenic in hollow organs, such as the ear or sinus, most bacteria must adhere to the mucosal lining. Viral infections that attack and damage mucosal linings of respiratory tracts may facilitate the ability of the bacteria to become pathogenic in the nasopharynx, eustachian tube, and middle ear cleft. […] Viral infection in the nasopharynx with subsequent inflammation of the orifice and mucosa of the eustachian tube has long been understood as part of the pathogenesis of AOM, although the complete role of the virus is not fully understood. […] The immunologic aspects of AOM are not confined to the middle ear. The nasopharynx plays an important role in the pathogenesis of AOM, and immunologic modifications in this lymphoid tissue provide some protection from pathogens by preventing their adherence to mucosal surfaces.

• #19 Middle Ear Inflammation (Otitis Media): Types, Causes, and Diagnosis

  https://www.healthline.com/health/otitis

  A middle ear infection or inflammation of the middle ear happens when a virus or bacteria inflames the area behind the eardrum. This is also known as otitis media and is most common in children. […] When the tube that connects the middle ear to the pharynx (eustachian tube) is blocked, fluid will collect behind the eardrum. Bacteria will often grow in the fluid, causing pain and inflammation. […] Acute otitis media may be treated with antibiotics, but OME is not typically accompanied by infection, so antibiotics are not helpful or necessary. […] Complications resulting from otitis media are rare but can occur. These complications include: infection that spreads to the bones of the ear (mastoiditis), infection that spreads to the fluid around the brain and spinal cord (meningitis), permanent hearing loss, ruptured eardrums.

• #20 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Acute otitis media is defined as an infection of the middle ear space. […] Infection of the middle ear can be viral, bacterial, or coinfection. The most common bacterial organisms causing otitis media are Streptococcus pneumoniae, followed by non-typeable Haemophilus influenzae(NTHi) and Moraxella catarrhalis. […] Otitis media begins as an inflammatory process following a viral upper respiratory tract infection involving the mucosa of the nose, nasopharynx, middle ear mucosa, and Eustachian tubes. Due to the constricted anatomical space of the middle ear, the edema caused by the inflammatory process obstructs the narrowest part of the Eustachian tube leading to a decrease in ventilation. This leads to a cascade of events resulting in an increase in negative pressure in the middle ear, increasing exudate from the inflamed mucosa, and buildup of mucosal secretions, which allows for the colonization of bacterial and viral organisms in the middle ear. The growth of these microbes in the middle ear then leads to suppuration and, eventually, frank purulence in the middle ear space.

• #21 Otitis Media (Acute) – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/middle-ear-and-tympanic-membrane-disorders/otitis-media-acute

  Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. […] The etiology of acute otitis media may be viral or bacterial. […] In neonates, gram-negative enteric bacilli, particularly Escherichia coli, and Staphylococcus aureus cause acute otitis media. […] In older infants and children 14 years, the most common organisms are Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and nontypeable Haemophilus influenzae; less common causes are group A beta-hemolytic streptococci and S. aureus. […] In patients 14 years, S. pneumoniae, group A beta-hemolytic streptococci, and S. aureus are most common, followed by H. influenzae. […] Complications of acute otitis media are uncommon. In rare cases, bacterial middle ear infection spreads locally, resulting in acute mastoiditis, petrositis, or labyrinthitis.

• #22 Optical Identification of Middle Ear Infection

  https://www.mdpi.com/1420-3049/25/9/2239

  Ear infection is one of the most commonly occurring inflammation diseases in the world, especially for children. Almost every child encounters at least one episode of ear infection before he/she reaches the age of seven. […] In this review paper, we present the various types of ear infection and the related pathogens responsible for middle ear infection. […] The three most common bacteria that are responsible for AOM and OME are Streptococcus pneumoniae (Gram-positive), Haemophilus influenza (Gram-negative), and Moraxella catarrhalis (Gram-negative). […] Fluid buildup in the middle ear with a moist and warm environment provides ready access and a well-suited place for bacterial growth and is the main cause of AOM. […] Accurate identification of bacteria will provide physicians additional information to prescribe the proper treatment plan while avoiding antimicrobial drug resistance.

• #23 Otitis Media (Acute) – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/middle-ear-and-tympanic-membrane-disorders/otitis-media-acute

  Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. […] The etiology of acute otitis media may be viral or bacterial. […] In neonates, gram-negative enteric bacilli, particularly Escherichia coli, and Staphylococcus aureus cause acute otitis media. […] In older infants and children 14 years, the most common organisms are Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and nontypeable Haemophilus influenzae; less common causes are group A beta-hemolytic streptococci and S. aureus. […] In patients 14 years, S. pneumoniae, group A beta-hemolytic streptococci, and S. aureus are most common, followed by H. influenzae. […] Complications of acute otitis media are uncommon. In rare cases, bacterial middle ear infection spreads locally, resulting in acute mastoiditis, petrositis, or labyrinthitis.

• #24 Acute Otitis Media: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/859316-overview

  The response is the establishment of an acute inflammatory reaction characterized by typical vasodilatation, exudation, leukocyte invasion, phagocytosis, and local immunologic responses within the middle ear cleft, which yields the clinical pattern of AOM. […] To become pathogenic in hollow organs, such as the ear or sinus, most bacteria must adhere to the mucosal lining. Viral infections that attack and damage mucosal linings of respiratory tracts may facilitate the ability of the bacteria to become pathogenic in the nasopharynx, eustachian tube, and middle ear cleft. […] Viral infection in the nasopharynx with subsequent inflammation of the orifice and mucosa of the eustachian tube has long been understood as part of the pathogenesis of AOM, although the complete role of the virus is not fully understood. […] The immunologic aspects of AOM are not confined to the middle ear. The nasopharynx plays an important role in the pathogenesis of AOM, and immunologic modifications in this lymphoid tissue provide some protection from pathogens by preventing their adherence to mucosal surfaces.

• #25

  https://link.springer.com/article/10.1007/s11882-010-0158-3

  Otitis media (OM) is the most prevalent childhood disease in developed countries. […] We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines. […] It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM. […] Bacterial infection is considered to be a dominant etiology, producing inflammation characterized by mucosal hyperplasia, effusion, and leukocytic infiltration of the middle ear. […] The present review focuses on the role of innate immunity in OM pathogenesis and recovery against the background that Toll-like receptor (TLR) deficiencies have been shown to induce significant abnormalities in the recovery from bacterial infection at other locations.

• #26

  https://link.springer.com/article/10.1007/s11882-010-0158-3

  TLRs are evolutionally conserved and act as the first line of host defense against infection. […] TLR activation results in the recruitment and activation of adaptor molecules, which include myeloid differentiation factor-88 (MyD88) and TIR domain containing adaptor inducing IFN- (TRIF). […] TLR signaling is critical for efficient host defense of the middle ear. […] Genes involved in innate immune responses were identified that, when absent, result in transition from the self-limiting characteristic of acute OM to persistent middle ear disease in mice. […] The effects of these gene defects underscore the importance of innate immune responses to the normal processes of OM resolution. […] The striking increase in duration of OM shows that MyD88 and TLR2 are particularly critical to the process of middle ear recovery from infection. […] In the absence of clearance, prolonged inflammation mediated by bacteria presumably leads to prolonged and increased hyperplasia and leukocyte recruitment. […] In summary, TLR signaling is critical for the timely resolution of bacterial OM.

• #27

  https://link.springer.com/article/10.1007/s11882-010-0158-3

  Inflammatory reactions associated with immune response to bacterial antigens, bacterial polysaccharides, and disorders of inflammatory pathways, such as the cytokine network and the complement cascade, may also contribute to OM pathogenesis, especially in its chronic forms. […] However, the central role of infection in OM suggests that immunity may be a key to OM resistance and resolution. […] Resistance to infection of the middle ear is the basis for avoidance of OM and, if infection ensues, recovery from middle ear disease. […] In contrast, existing systemic immunity is very strongly expressed in the middle ear. […] It can be presumed that this is also true in the middle ear, and deficiencies in innate immunity might be expected to lead to increased incidence, severity, and duration of OM.

• #28 Advances in Treating Middle Ear Infections in Children | The Hearing Review

  https://hearingreview.com/hearing-products/accessories/components/advances-in-treating-middle-ear-infections-in-children

  The researchers at HEI have hypothesized that inflammation and mucus overproduction are caused by bacteria through specific signal transduction pathways. […] In a recent report published in the July 2001 issue of Proceedings of the National Academy of Sciences, Li and his research team provided clear evidence that bacteria induce the inflammation by activating a key signaling protein, called p38 MAP kinase. […] Further, it was found that bacteria also stimulate mucus overproduction through activation of the same signaling protein. […] These studies open up novel therapeutic targets for the treatment of middle ear infection. […] The research has demonstrated, for the first time, that proteins produced by cells of the middle ear do kill otitis media pathogens. […] By understanding the origins and roles of the naturally occurring antimicrobial peptides and proteins, researchers are uncovering new approaches to treat middle ear infections, based on the bodys innate ability to fight bacteria. […] Scientists are also studying the signal transduction pathways through which bacteria cause inflammation and mucus overproduction.

• #29 Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7062565/

  Non-typeable strains of Haemophilus influenzae (NTHi) have continued to grow as important causative agents of OM and other respiratory infections over the past four years. […] Biofilms including both bacteria and viruses are a key component of both single species and polymicrobial OM pathogenesis and are highly responsive to environmental factors. It is common to isolate multiple organisms from the middle ears of patients with OM. […] Otopathogens have been demonstrated to organize into biofilms within the nasopharynx and the middle ear and this is important in disease persistence and chronicity. The importance of biofilm formation for the pathogen is exemplified by the in vivo production of molecules such as autoinducers that promote biofilm formation, prevent dispersal and increase persistence.

• #30 Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7062565/

  The requirement for inflammation has been demonstrated in the AOM chinchilla model where chinchillas were infected with S. pneumoniae and three different adenoviruses. Infection with a wild-type adenovirus or a hyperinflammatory adenovirus increased the proportion of ears identified as culture positive for S. pneumoniae compared to animals infected with bacteria alone. […] Since the introduction of pneumococcal conjugate vaccines, we have seen the emergence of non-encapsulated pneumococcal variants (also referred to in some studies as nontypeable). Studies have demonstrated that non-encapsulated pneumococci can colonize and persist within the nasopharynx, and also have the capacity to persist within the middle-ear chamber in the chinchilla. […] Non-encapsulated pneumococci have also been shown to persist within polymicrobial biofilms and cause OM in conjunction with NTHi.

• #31 Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7062565/

  Non-typeable strains of Haemophilus influenzae (NTHi) have continued to grow as important causative agents of OM and other respiratory infections over the past four years. […] Biofilms including both bacteria and viruses are a key component of both single species and polymicrobial OM pathogenesis and are highly responsive to environmental factors. It is common to isolate multiple organisms from the middle ears of patients with OM. […] Otopathogens have been demonstrated to organize into biofilms within the nasopharynx and the middle ear and this is important in disease persistence and chronicity. The importance of biofilm formation for the pathogen is exemplified by the in vivo production of molecules such as autoinducers that promote biofilm formation, prevent dispersal and increase persistence.

• #32 Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7062565/

  Non-typeable strains of Haemophilus influenzae (NTHi) have continued to grow as important causative agents of OM and other respiratory infections over the past four years. […] Biofilms including both bacteria and viruses are a key component of both single species and polymicrobial OM pathogenesis and are highly responsive to environmental factors. It is common to isolate multiple organisms from the middle ears of patients with OM. […] Otopathogens have been demonstrated to organize into biofilms within the nasopharynx and the middle ear and this is important in disease persistence and chronicity. The importance of biofilm formation for the pathogen is exemplified by the in vivo production of molecules such as autoinducers that promote biofilm formation, prevent dispersal and increase persistence.

• #33 Bacteria Hiding Out Inside Epithelial Cells May Promote Recurring Ear Infections – Pediatrics Nationwide

  https://pediatricsnationwide.org/2019/01/10/bacteria-hiding-out-inside-epithelial-cells-may-promote-recurring-ear-infections/

  By using short periods of heme-iron restriction when culturing NTHI, we can model nutritional immunity in a lab setting to investigate how adaptation to nutrient restriction affects NTHI pathogenesis. […] Our research team, co-headed by Kevin Mason, PhD, and Sheryl Justice, PhD, principal investigators in the Center for Microbial Pathogenesis, recently published two studies demonstrating a role for bacterial adaptation to nutrient limitation in inducing persistence and survival of NTHI as an intracellular pathogen inside middle ear epithelial cells. […] It’s an exciting and unexpected finding that NTHI can adapt to heme-iron starvation and then survive inside the cells of the middle ear in what are known as intracellular bacterial communities (IBCs). […] The study recently published in mSphere found that culturing NTHI under conditions of transient heme-iron restriction promotes invasion of NTHI into epithelial cells and subsequent escape from endocytic pathways that would typically result in bacterial killing in the cell.

• #34 Otopathogenic Staphylococcus aureus Invades Human Middle Ear Epithelial Cells Primarily through Cholesterol Dependent Pathway | Scientific Reports

  https://www.nature.com/articles/s41598-019-47079-7

  Chronic suppurative otitis media (CSOM) is one of the most common infectious diseases of the middle ear especially affecting children, leading to delay in language development and communication. […] Although Staphylococcus aureus is the most common pathogen associated with CSOM, its interaction with middle ear epithelial cells is not well known. […] In the present study, we observed that otopathogenic S. aureus has the ability to invade human middle ear epithelial cells (HMEECs) in a dose and time dependent manner. […] We observed that otopathogenic S. aureus primarily employs a cholesterol dependent pathway to colonize HMEECs. […] The results of the present study provide new insights into the pathogenesis of S. aureus induced CSOM. […] Although there is no consensus, it has been hypothesized that the invasion of middle ear epithelial cells (MEECs) may play a crucial role in the pathogenesis of CSOM.

• #35 Bacteria Hiding Out Inside Epithelial Cells May Promote Recurring Ear Infections – Pediatrics Nationwide

  https://pediatricsnationwide.org/2019/01/10/bacteria-hiding-out-inside-epithelial-cells-may-promote-recurring-ear-infections/

  Using UPEC as a paradigm, it’s tempting to speculate that life inside the epithelial cells may protect NTHI from the body’s immune defenses and/or antibacterial therapies and could ultimately promote reinfection or recurrence of OM. […] However, we still needed to understand what benefit the IBC confers to NTHI and how it drives persistence and recurring infection. […] To that end, the second, related study recently published in PLoS Pathogens described the identification of a mutation that NTHI acquires after transient heme restriction. […] Our studies link a mutation in icc with significantly increased long-term survival of NTHI in culture as well as with a higher IBC count during infection in the preclinical model. […] The results of these studies begin to provide novel insight as to why some kids might struggle with recurring ear infections, and reveal a new avenue for investigating ways to eradicate intracellular NTHI.

• #36 Otopathogenic Staphylococcus aureus Invades Human Middle Ear Epithelial Cells Primarily through Cholesterol Dependent Pathway | Scientific Reports

  https://www.nature.com/articles/s41598-019-47079-7

  In the present study, we examined the ability of otopathogenic S. aureus to invade human middle ear epithelial cells (HMEECs), in vitro. […] We observed that otopathogenic S. aureus can invade HMEECs in a time and dose dependent manner that is primarily dependent on cholesterol pathway. […] Our results demonstrate for the first time that S. aureus is able to invade HMEECs that can contribute to its capability to induce CSOM by evading host immune responses. […] Our data also suggest that cholesterol and lipid rafts play an important role in internalization of S. aureus by HMEECs.

• #37 Otopathogenic Staphylococcus aureus Invades Human Middle Ear Epithelial Cells Primarily through Cholesterol Dependent Pathway | Scientific Reports

  https://www.nature.com/articles/s41598-019-47079-7

  Chronic suppurative otitis media (CSOM) is one of the most common infectious diseases of the middle ear especially affecting children, leading to delay in language development and communication. […] Although Staphylococcus aureus is the most common pathogen associated with CSOM, its interaction with middle ear epithelial cells is not well known. […] In the present study, we observed that otopathogenic S. aureus has the ability to invade human middle ear epithelial cells (HMEECs) in a dose and time dependent manner. […] We observed that otopathogenic S. aureus primarily employs a cholesterol dependent pathway to colonize HMEECs. […] The results of the present study provide new insights into the pathogenesis of S. aureus induced CSOM. […] Although there is no consensus, it has been hypothesized that the invasion of middle ear epithelial cells (MEECs) may play a crucial role in the pathogenesis of CSOM.

• #38 Otopathogenic Staphylococcus aureus Invades Human Middle Ear Epithelial Cells Primarily through Cholesterol Dependent Pathway | Scientific Reports

  https://www.nature.com/articles/s41598-019-47079-7

  In the present study, we examined the ability of otopathogenic S. aureus to invade human middle ear epithelial cells (HMEECs), in vitro. […] We observed that otopathogenic S. aureus can invade HMEECs in a time and dose dependent manner that is primarily dependent on cholesterol pathway. […] Our results demonstrate for the first time that S. aureus is able to invade HMEECs that can contribute to its capability to induce CSOM by evading host immune responses. […] Our data also suggest that cholesterol and lipid rafts play an important role in internalization of S. aureus by HMEECs.

• #39 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Several risk factors can predispose children to develop acute otitis media. The most common risk factor is a preceding upper respiratory tract infection. Other risk factors include male gender, adenoid hypertrophy (obstructing), allergy, daycare attendance, environmental smoke exposure, pacifier use, immunodeficiency, gastroesophageal reflux, parental history of recurrent childhood OM, and other genetic predispositions. […] In serous acute otitis media (SAOM), inflammation of the middle ear and the eustachian tube has been identified as the major precipitating factor. Venous or lymphatic stasis in the nasopharynx or the eustachian tube plays a vital role in the pathogenesis of AOM. Inflammatory cytokines attract plasma cells, leukocytes, and macrophages to the site of inflammation.

• #40 Otitis Media: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/1001/p435.html/1000

  Acute otitis media is usually a complication of eustachian tube dysfunction that occurs during a viral upper respiratory tract infection. […] Bacteria can be isolated from middle ear fluid cultures in 50% to 90% of cases of AOM and OME. […] Risk factors for AOM are listed in Table 1. […] An AOM diagnosis requires moderate to severe bulging of the tympanic membrane, new onset of otorrhea not caused by otitis externa, or mild bulging of the tympanic membrane associated with recent onset of ear pain (less than 48 hours) or erythema. […] OME is defined as middle ear effusion in the absence of acute symptoms. […] Inflammation with bulging of the tympanic membrane on otoscopy is highly predictive of AOM. […] Antibiotic therapy for AOM is often associated with diarrhea. […] Children with persistent, significant AOM symptoms despite at least 48 to 72 hours of antibiotic therapy should be reexamined.

• #41

  https://bpac.org.nz/2022/otitis-media.aspx

  Otitis media is defined as inflammation of the middle ear and is classified into three categories: Acute otitis media (AOM; most common): acute inflammation and effusion of the middle ear, with rapid onset of symptoms and signs consistent with an ear infection; in younger children, symptoms may be non-specific […] Otitis media is characterised by middle ear and tympanic membrane inflammation resulting from an upper respiratory tract infection due to viral (e.g. respiratory syncytial virus, rhinovirus, influenza viruses, adenovirus) or bacterial infection (e.g. Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis), or a combination of both. […] Factors influencing the risk of a child developing otitis media are divided into individual or environmental and may be modifiable or non-modifiable.

• #42 Otitis Media (Middle Ear Infections) | ENT & Allergy of Delaware

  https://entad.org/resources/patient-information-dr-teixido/otitis-media-middle-ear-infections/

  The pressure always remains equalized this way. […] With recurrent ear infections, the eardrum (tympanic membrane) may become scarred. […] Repeated infections may also impair the delicate motions of the middle ear bones so that they become stiff or even stuck. […] Toxins from infections can diffuse through a membrane called the round window into the fluids of the inner ear. […] Infections can spread from the middle ear to the brain through direct erosion of this bone, through pre-existing defects in the bone, through the inner ear, or through nearby blood or lymphatic vessels.

• #43 Can Ear Infections Cause Hearing Loss? – Orange Coast ENT

  https://www.entdoctoroc.com/blog/can-ear-infections-cause-hearing-loss/

  Ear infections occur in different parts of the ear. The most common type impacts the middle ear—the space located just behind the eardrum. This area is normally filled with air, but during an infection, fluid and inflammation can build up, hindering the eardrum’s ability to vibrate. This restricted movement of the eardrum reduces the transmission of sound waves, leading to temporary hearing difficulties. […] Ear infections often lead to temporary hearing loss, but in some cases, it can be permanent. The type of hearing loss experienced generally depends on the severity and duration of the infection. […] Fluid accumulation behind the eardrum, inflammation in the middle ear, and infection can hinder sound transmission through the ear’s delicate structures. This buildup of fluid or inflammation can block or dampen the movement of the eardrum and the three tiny bones in the middle ear (ossicles), which are responsible for carrying sound vibrations to the inner ear.

• #44 Middle Ear Inflammation (Otitis Media): Types, Causes, and Diagnosis

  https://www.healthline.com/health/otitis

  A middle ear infection or inflammation of the middle ear happens when a virus or bacteria inflames the area behind the eardrum. This is also known as otitis media and is most common in children. […] When the tube that connects the middle ear to the pharynx (eustachian tube) is blocked, fluid will collect behind the eardrum. Bacteria will often grow in the fluid, causing pain and inflammation. […] Acute otitis media may be treated with antibiotics, but OME is not typically accompanied by infection, so antibiotics are not helpful or necessary. […] Complications resulting from otitis media are rare but can occur. These complications include: infection that spreads to the bones of the ear (mastoiditis), infection that spreads to the fluid around the brain and spinal cord (meningitis), permanent hearing loss, ruptured eardrums.

• #45 Advances in Treating Middle Ear Infections in Children | The Hearing Review

  https://hearingreview.com/hearing-products/accessories/components/advances-in-treating-middle-ear-infections-in-children

  Chronic otitis media with effusion is the leading cause of conductive hearing loss in children and may hamper early speech and language development. […] There has been great progress made toward clarifying the molecular basis of the pathogenesis of otitis media and developing new therapeutic ways to combat this disease. […] Recently, researchers have uncovered the pathological processes underlying this disease, and for the first time shown that proteins produced by cells of the middle ear do kill otitis media pathogens. […] The protraction of the inflammatory process in the middle ear can lead to the development of chronic otitis media with effusion. […] The dramatic increase in cases of chronic otitis media occurred after the introduction of antibiotics, which is still the most common treatment for acute otitis media.

• #46 Advances in Treating Middle Ear Infections in Children | The Hearing Review

  https://hearingreview.com/hearing-products/accessories/components/advances-in-treating-middle-ear-infections-in-children

  Scientists and physicians at the House Ear Institute (HEI) and House Ear Clinic are working with Childrens Hospital of Los Angeles to enhance understanding about otitis media and to find ways of reducing the severity of this disease. […] Towards this goal, the molecular basis of the pathogenesis of otitis media is being sought, with the hope that the research will lead to the discovery of novel methods of treatment to complement and/or replace the antibiotics currently being prescribed. […] An HEI research team led by co-author Jian-Dong Li, MD, PhD, in the Section on Signal Transduction is studying the sequence of events that is set into motion as a result of the binding of bacteria to cells of the middle ear. […] The work of these researchers has identified the cell signaling pathways through which bacteria cause inflammation and mucus overproduction in the middle ear, and thus lead to the development of conductive hearing loss.

• #47 Advances in Treating Middle Ear Infections in Children | The Hearing Review

  https://hearingreview.com/hearing-products/accessories/components/advances-in-treating-middle-ear-infections-in-children

  The researchers at HEI have hypothesized that inflammation and mucus overproduction are caused by bacteria through specific signal transduction pathways. […] In a recent report published in the July 2001 issue of Proceedings of the National Academy of Sciences, Li and his research team provided clear evidence that bacteria induce the inflammation by activating a key signaling protein, called p38 MAP kinase. […] Further, it was found that bacteria also stimulate mucus overproduction through activation of the same signaling protein. […] These studies open up novel therapeutic targets for the treatment of middle ear infection. […] The research has demonstrated, for the first time, that proteins produced by cells of the middle ear do kill otitis media pathogens. […] By understanding the origins and roles of the naturally occurring antimicrobial peptides and proteins, researchers are uncovering new approaches to treat middle ear infections, based on the bodys innate ability to fight bacteria. […] Scientists are also studying the signal transduction pathways through which bacteria cause inflammation and mucus overproduction.

• #48 Advances in Treating Middle Ear Infections in Children | The Hearing Review

  https://hearingreview.com/hearing-products/accessories/components/advances-in-treating-middle-ear-infections-in-children

  The researchers at HEI have hypothesized that inflammation and mucus overproduction are caused by bacteria through specific signal transduction pathways. […] In a recent report published in the July 2001 issue of Proceedings of the National Academy of Sciences, Li and his research team provided clear evidence that bacteria induce the inflammation by activating a key signaling protein, called p38 MAP kinase. […] Further, it was found that bacteria also stimulate mucus overproduction through activation of the same signaling protein. […] These studies open up novel therapeutic targets for the treatment of middle ear infection. […] The research has demonstrated, for the first time, that proteins produced by cells of the middle ear do kill otitis media pathogens. […] By understanding the origins and roles of the naturally occurring antimicrobial peptides and proteins, researchers are uncovering new approaches to treat middle ear infections, based on the bodys innate ability to fight bacteria. […] Scientists are also studying the signal transduction pathways through which bacteria cause inflammation and mucus overproduction.

• #49 Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear | Scientific Reports

  https://www.nature.com/articles/srep22663

  Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. […] We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. […] Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. […] Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. […] The primary function of the TM is to collect and transmit sound from the ear canal through the ossicles of the air-filled ME to the inner ear. It also functions as a barrier to air pressure and fluids and protects the ME from foreign substances and infective organisms. […] The impermeable nature of the TM is determined largely by its epithelia, since the connective tissue fibers of the middle layer do not appear to form a continuous layer at the molecular level, which isolate the ME from the external ear canal.

• #50 Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear | Scientific Reports

  https://www.nature.com/articles/srep22663

  However, the cells of both the outer and inner epithelia of the TM are connected to one another by tight junctions. […] These junctions maintain the TMs air, fluid and molecular barrier function. […] Therefore, local application of drugs to the middle and inner ear requires disruption of TM integrity, either by needle injection or by insertion of a tympanostomy tube that provides a relatively stable opening. […] In this study, we hypothesized that proteins might mediate a biological mechanism of active transport across the TM and that sequential selection of phage-display libraries would identify rare but novel peptides that actively cross into the ME without damaging the TM. […] The transport mechanism used by the targeted phage is biologically active, in that binding internalization and translocation are dose, temperature and time dependent.

• #51 Acute Otitis Media – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470332/

  Acute otitis media is defined as an infection of the middle ear space. […] Infection of the middle ear can be viral, bacterial, or coinfection. The most common bacterial organisms causing otitis media are Streptococcus pneumoniae, followed by non-typeable Haemophilus influenzae(NTHi) and Moraxella catarrhalis. […] Otitis media begins as an inflammatory process following a viral upper respiratory tract infection involving the mucosa of the nose, nasopharynx, middle ear mucosa, and Eustachian tubes. Due to the constricted anatomical space of the middle ear, the edema caused by the inflammatory process obstructs the narrowest part of the Eustachian tube leading to a decrease in ventilation. This leads to a cascade of events resulting in an increase in negative pressure in the middle ear, increasing exudate from the inflamed mucosa, and buildup of mucosal secretions, which allows for the colonization of bacterial and viral organisms in the middle ear. The growth of these microbes in the middle ear then leads to suppuration and, eventually, frank purulence in the middle ear space.

• #52 Otitis Media: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/994656-overview

  Otitis media (OM) is any inflammation of the middle ear, without reference to etiology or pathogenesis. It can be classified into many variants on the basis of etiology, duration, symptomatology, and physical findings. […] The most important factor in middle ear disease is eustachian tube (ET) dysfunction (ETD), in which the mucosa at the pharyngeal end of the ET is part of the mucociliary system of the middle ear. Interference with this mucosa by edema, tumor, or negative intratympanic pressure facilitates direct extension of infectious processes from the nasopharynx to the middle ear, causing OM. […] In children, developmental alterations of the ET, an immature immune system, and frequent infections of the upper respiratory mucosa all play major roles in AOM development. Studies have demonstrated how viral infection of the upper respiratory epithelium leads to increased ETD and increased bacterial colonization and adherence in the nasopharynx.

• #53 Acute otitis media in adults – UpToDate

  https://www.uptodate.com/contents/acute-otitis-media-in-adults-suppurative-and-serous

  Eustachian tube dysfunction, commonly related to seasonal allergic rhinitis or upper respiratory tract infection, is the most important factor in the pathogenesis of middle ear infections in adults. […] Eustachian tube dysfunction is the most important factor in the pathogenesis of middle ear infections in both childhood and adulthood. Eustachian tube dysfunction induces a relative negative pressure in the middle ear space, with the lack of aeration and accumulation of fluid providing an environment conducive to the development of AOM or otitis media with effusion. […] The infection is most frequently precipitated by impaired function of the Eustachian tube, resulting in the retention and suppuration of retained secretions.

• #54 Management of acute otitis media in children six months of age and older | Canadian Paediatric Society

  https://cps.ca/documents/position/acute-otitis-media

  AOM is extremely common, and 75% of children experience at least one ear infection before starting school. […] ET dysfunction or obstruction due to a viral infection or other causes of mucosal inflammation can impair this normal mechanism. The lack of middle ear drainage leads to fluid stasis and, if the fluid is colonized with bacterial and/or viral pathogens, can lead to AOM. […] A small proportion of children have lower levels of secretory immunoglobulin A or persistent biofilms in the middle ear, which may play a role in increasing the risk for recurrent AOM. […] There is a clinical spectrum of middle ear infections associated with the initiation and progression of infection leading to bacterial AOM. […] The most common bacteria causing AOM are S pneumoniae, H influenzae, M catarrhalis and (less commonly) GAS.

• #55 The unsolved problem of otitis media in indigenous populations: a systematic review of upper respiratory and middle ear microbiology in indigenous children with otitis media | Microbiome | Full Text

  https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0577-2

  Otitis media (OM) imposes a great burden of disease in indigenous populations around the world, despite a variety of treatment and prevention programs. Improved understanding of the pathogenesis of OM in indigenous populations is required to advance treatment and reduce prevalence. […] Otitis media (OM) describes a spectrum of pathologies that involve inflammation and/or infection in the middle ear. This spectrum encompasses a continuum from acute to chronic disease that is clinically characterized by fluid in the middle ear. […] The reasons for high OM prevalence in indigenous populations are likely to be multi-factorial. Risk factors include poverty, inadequate housing, overcrowding, and exposure to environmental tobacco smoke. […] While high rates of OM are reported for many developing countries, indigenous populations, as defined by the United Nations, share unique challenges in relation to OM. Otitis media in indigenous populations is difficult to prevent and treat, therefore we need to gain a better understanding of the microbial pathogenesis to establish knowledge gaps, provide direction for future research, and help guide appropriate prevention and treatment options.

Zobacz więcej