OTITIS MEDIA

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• OTITIS MEDIA
• Definities terminologie klassificatie
• Diagnose
• Epidemiologie
• Bacteriologie
• Pathofysiologie
• Natuurlijk verloop en therapie

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Introduction the burden of otitis media

• Egyptian mummies have perforations of TM and
  mastoid destruction
• 3.5 billion in expenditures in USA
• Most common reason for visit to pediatrician
• In the developed world AOM is the most common
  cause for prescribing antibiotics in children and
  accounts for over 90 of all antimicrobial
  consumption during the first 2 years of life
  (Dagan, 1995).
• Tympanostomy tube placement is 2nd most common
  surgical procedure in children
• Development of multidrug-resistant bacteria

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1. Definition, Terminology, Classification

• Otitis media inflammation of the middle ear
  without reference to etiology or pathogenesis
• Acute otitis media inflammation of the middle
  ear with rapid onset of one or more local or
  systemic signs and symptoms of acute infection
  within the middle ear (otalgia, otorrhea, fever,
  anorexia, vomiting or diarrhea)
• Acute otitis media without effusion (myringitis)
  erythema and opacification of the eardrum. Blebs
  or bullae may be present.
• Recurrent otitis media (5 to 10 of children)
• gt 3 episodes of AOM in 3 months with evidence of
  cure between episodes
• gt 4 episodes of AOM in 6 months

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Normaal TV
Acute otitis media
Acute otitis media
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Definition, Terminology, Classification

• Otitis media with effusion (SOM, OME)
  inflammation of middle ear with liquid collected
  in middle-ear space. Signs and symptoms of acute
  infection are absent no perforation of the
  tympanic membrane
• Middle-ear effusion liquid in middle ear.
  Effusion may be serous (thin watery liquid),
  mucoid (thick viscid mucus-like liquid), purulent
  or a combination of these
• An effusion can result from AOM or OME. It can be
  of recent onset, acute, or long-lasting, subacute
  or chronic.

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Otitis media met efusie secretoire otitis
media glue ear
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Definition, Terminology, Classification

• Eustachian Tube dysfunction middle ear disorder
  that can have symptoms similar to those of otitis
  media such as hearing loss, otalgia and tinnitus,
  but with no middle ear effusion. The dysfunction
  may be related to an Eustachian tube that is too
  closed (i.e. obstructed) or too open (i.e.
  patulous).
• The latter condition is most frequently
  associated with symptoms of autophony.

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Acute Otitis Media
Resolution
Suppurative Complication
Acute PerforationOtitis Media
Persistent Effusion
CSOM
Resolution
Chronic OME
ResolutionHealing
Resolution Chronic Perforation
Sequelae
Resolution
Perforation SOM
No Otitis Media
Recurrent Otitis Media
CSOM
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2. Diagnosis

• Accurate diagnosis is important to avoid
  unnecessary treatment !
• 1. Medical history
• 2. Physical examination

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Diagnosis Medical history

• Otalgia most common, ear pulling, irritability
• Otorrhea
• Hearing loss
• Fever
• Preceding upper respiratory tract infection
• Purulent conjunctivitis (Haemophilus influenzae)
• Vertigo not common as a complaint, unilateral
  disease, clumsiness
• Nystagmus labyrinthitis !
• Tinnitus
• Swelling about the ear dd mastoiditis, external
  otitis, adenitis
• Facial paralysis

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Diagnosis

• AOM
• preceding URI
• fever
• otalgia
• otorrhea
• hearing loss

• OME
• possible asymptomatic
• hearing loss
• plugged
• popping

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Diagnosis Physical examination

• Adequate examination of the head and neck region
  !
• associated exanthema
• predisposing factors
• alarm symptoms

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Diagnosis otoscopy
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3. Epidemiology Cumulative incidence of otitis
media
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Epidemiology risk factors

• I. Host-Related factors (intrinsic)
• Age
• gender males more prone to persistent MEE
• race american natives and inuits gt whites gt
  blacks
• cleft palate/craniofacial abnormality/Down
  Syndrome
• genetic
• allergy and immunity

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• Age
• highest incidence of AOM between 6 months and 11
  months of age
• onset of first episode before 6 months of age is
  strong predictor for recurrent OM
• risk for persistent MEE after AOM inversely
  correlated with age (gt4 times when lt 2 years of
  age)

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• Cleft palate/Craniofacial abnormality/Down
  Syndrome
• OM is present in nearly all infants under 2 years
  of age with unrepaired clefts of the palate
• occurrence reduces following surgical repair
• Children with Down poor active opening function
  of ET, low resistance of tube

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• Genetic
• predisposition to recurrent episodes of AOM and
  chronic MEE may have a significant genetic
  component suggested by anatomic, physiologic and
  epidemiologic data
• twin studies (Norway, Pittsburg)
• familial clustering
• genetic markers G2m(23) associated with rAOM

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• 2. Environmental factors (extrinsic)
• season and upper respiratory infection
• day care / home care
• siblings
• passive smoking (Etzel et al.)
• breast feeding / bottle feeding
• socio-economic status
• pacifier use

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Relatie seizoen en prevalentie van otitis media
WETTEREN
Van Cauwenberge, 1989
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Mean total number of acute RTI diagnosis in
children attending different types of day-care
during the second and third years of life (N113)
1.4 - 1.2 - 1 - 0.8 - 0.6 - 0.4 - 0.2 - 0 -
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OM - smoke exposure

• Induces changes in respiratory tract
• Increased dysfunction of ET, otorrhea, chronic
  and recurrent AOM in children with history of
  parental smoking

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4. Microbiology

• S. pneumoniae 50-55
• H. influenzae - 20-25 infernal trio
• M. catarrhalis - 10-15
• Group A strep - 2-4
• Staph Aureus ?
• Infants higher incidence of gram negative
  bacilli

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Kweek Viraal 48 Pitkaranta et
al. 52 Galveston et al. Respiratory
syncytial virus Parainfluenza virus Influenza
virus Rhinovirus coronavirus

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Chronic MEE

• previously thought sterile
• 30-50 grow in culture
• over 75 PCR
• usual organisms

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5. Pathogenesis of OM
ET dysfunction
Infection
Host respons Liberation of inflammatory mediators
Increase of vascular permeability Increase of
glandular secretion
Inflammation
Mucosal proliferation
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1. Role of the Eustachian Tube
1. Pressure regulation of middle ear 2. Clearance
Drainage of middle ear secretions mucociliary mu
scular 3. Protection from sound and secretion
anatomic immunologic and mucociliairy
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Developmental Differences between Infants and
Adults in Anatomy of the Eustachian Tube

• Adults
• ant 2/3- cartilaginous
• post 1/3- bony
• 45 degree angle
• nasopharyngeal orifice 8-9 mm

• Children
• longer bony portion
• 10 degree angle
• nasopharyngeal orifice 4-5 mm in infants

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Eustachian tube

• Usually closed
• Opens during swallowing, yawning, and sneezing
• Opening involves cartilaginous portion
• Tensor veli palatini responsible for active tubal
  opening
• No constrictor function

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Dysfunction 1. Impairment of pressure
regulation
Functional obstruction
Obstruction
Weak TVP
Anatomic obstruction
After Bluestone
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Dysfunction 2. Impairment of clearance
Mucociliary - all children with amotile
ciliary syndrome (Kartagener s) develop OM -
viral URTI causes destruction of ciliated cells
and therefore predisposes to bacterial OM
Muscular Animal models section of TVP
botox, cleft palate
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Dysfunction 3. Loss of protective function
Anatomic Abnormal patency Short tube
Abnormal gas pressures intratympanic,
nasopharyngeal Non intact middle
ear-mastoid Immunologic Secretory system
Mucines, Aquaporins, Cytokines Innate
immunity
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Infection
ET dysfunction
Host respons Liberation of inflammatory mediators
Increase of vascular permeability Increase of
glandular secretion
Inflammation
Mucosal proliferation
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Cumulative acquisition rate of pathogens during
first year
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• Cumulative acquisition rates of pathogens during
  first year of life( Faden et al., 1997)
• rapid increase in the first 6 months of life
• 68 of children colonized with 1 or more
  pathogens after 6 months
• colonization rates
• M.cattharalis (55)gtS.pneumoniae (38) gt NTHi
  (19)

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Relationship between frequency of colonization
and number of AOM
Episodes of otitis media
Faden et al., 1997
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• Factors affecting colonization rates
• Season
• Number of siblings
• Day care
• Respiratory illness
• Genetic (HLA-A2).(Kalm,1994)
• Immunology

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• Pathofysiology (1) Development of otitis media
• Pathogens must adhere to nasopharyngeal
  epithelium
• Pathogens must enter the ME cavity through the
  Eustachian tube (ET)
• Pathogens must be able to withstand and
  overcome the defensive mechanisms of tubotympanum
• Viruses, IgE-mediated hypersensitivity , overuse
  (inadequate) use of antibiotics, may trigger
  changes in nasopharyngeal flora leading to
  otitis media.

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• Pathofysiology (2) Development of otitis media
• The normal tubotympanum is protected by the
  mucociliary system and the secreted molecules of
  innate immunity.
• During infections, these systems provide the
  critical first line of defense before the
  activation of adaptive immunity
• The development of specific mucosal immunity
  against these bacteria may be under genetic
  control.

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Pathofysiology (3) Development of otitis media

• There are many reasons why the Eustachius tube
  may be dysfunctional. The clinician should
  determine the most likely etiology to direct
  management decisions.
• Since there is now evidence that upper
  respiratory tract infections can precede an
  episode of either acute otitis media or otitis
  media with effusion, management should be focused
  of prevention of these viral infections

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6. Treatment

• 6.1 Treatment Acute otitis media
• Goals
• Decreasing the duration of fever and pain
• Expediting the resumption of normal activity
• Limiting the small potential for suppurative
  complications

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• Spontaneous cure in up to 80 percent of children
  treated only with analgesics
• Antibiotics increase cure rate to 94 percent, and
  decrease duration of symptoms and risk of
  complications
• Broad spectrum antibiotics probably offer no
  advantages over standard antimicrobials

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• Take into account
• History of allergy or intolerance to a particular
  antibiotic or class of antibiotic
• Presumed causative organism (Streptococcus
  pneumoniae is most likely in a child previously
  untreated for AOM)

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• Take into account
• Antibiotic exposure within the previous 30 days
  may have caused resistant organisms to
  predominate
• Conjunctivitis/Otitis Syndrome is suggestive of
  H. influenzae infection

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Worldwide view of resistance to S.pneumoniae
Steele RW, 1995
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Evolution of penicillin-resistance (I R, ) in
pneumococci for common infections (1989 - 2000)
in Belgium
Penicillin
R
Verhaegen et al.
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Problem of Resistance

• Strep. Pneumoniae
• Target resistance
• H. influenzae and M. catarrhalis
• beta-lactamase production
• All M. catarrhalis
• 15-25 of H. influenzae
• Clavulanic acid

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Blinde start (empirische therapie) of na (kweek)
antibiogram ?

•  Blind 
• Vooral in routine, ongecompliceerde infectie,
  goed gedocumenteerd in (rec) literatuur
• Op basis va kweek/antibiogram
• Vooral indien ernstig, herhaaldelijk, mislukking
  (verwekker/antibiogram onvoorspelbaar)

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• Follow-up
• Once antibiotic treatment is initiated the child
  should demonstrate symptomatic benefit within 72
  hours
• Failure to show improvement indicates need for
  re-evaluation.
• A follow-up examination should be scheduled for
  one month after the diagnosis and should include
• - Inspection of the tympanic membrane
• - Assessment of hearing

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• Follow-up
• The purpose of the follow-up exam is to identify
  persistent otitis media or persistent middle ear
  effusion
• Children with persistent otitis media or
  persistent middle ear effusion should be seen on
  a monthly basis until their exam is normal

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• 6.2 Treatment Recurrent Otitis media
• Chemoprophylaxis
• Sulfisoxazole, amoxicillin, ampicillin
• less efficacy for intermittent propylaxis
• Myringotomy and tube insertion
• Decreased frequency and severity of AOM
• otorrhea and other complications
• may require prophylaxis if severe
• Adenoidectomy
• 28 and 35 fewer episodes of AOM at first and
  second years

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• 6.3 Treatment Recurrent Otitis media
• Spontaneous resolution rates for OME
• OME persisting after AOM 1m 60 (55-65)
• 3m 74 (67-80)
• OME of unspecified duration lt1m 52 (47-58)
• 2-3m 63 (60-66)
• 4-6m 76 (73-79)
• 7-9m 82 (79-86)
• 10-12m 88 (84-90)
• 13-15m 92 (89-95)
• 16-24m 97 (95-99)

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Natural history of OME

• Extremely dynamic course of OME 30-40 of
  children have recurrent episodes
• Spontaneous resolution depending on seasonal
  variation
• Seasonal trends lt important in long-term cases

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Natural history of OME

• 1. Most OME resolves within a few months,
  prognosis inversely related to duration newly
  diagnosed OME does extremely well, OME lasting
  weeks or months does poorly
• 2. The chance of spontaneous resolution
  diminishes greatly after 3-6 months

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Medical therapy

• 1. Antibiotic therapy of OME has a modest impact
  on short-term resolution
• 2. The impact on long-term resolution is smaller,
  if not negligible (Mandel, Giebink)
• 3. Steroid therapy and antihistamine-decongestant
  therapy have no proven effect on resolution of
  OME

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Surgical therapy

• Ventilation tubes
• Adenoidectomy
• Maw, 1993
• Beneficial effect of tubes or adenoidectomy
  compared with no surgery
• Further improvement when combination of tubes and
  adenoidectomy
• Gates, 1987
• After adenoidectomy
• significant less time with effusion
• longer time to first recurrence
• fewer surgical re-treatments

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100 90 80 70 60 50 40 30 20 10 0
0 1 2 3 4 5 6 7 8 9 10

• No surgery (n77)
• Ventilation tube only
• (n77)
• Adenoidectomy only
• Adenoidectomy
• and tube (n136)

Proportion () with fluid remaining
Survival functions for time to fluid Clearance as
Confirmed by otoscopy
Years
Maw et al, 1994
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Tympanostomy tube insertion

• Unresponsive OME gt3 months bilaterally, or gt 6
  months unilateral, sooner if associated hearing
  problems
• Recurrent MEE with excessive cumulative duration
• Speech language delay
• Recurrent AOM - gt3/6 monthss or gt4/12 months
• Eustachian tube dysfunction
• Suppurative complication
• Severe tympanic membrane retraction

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Inconveniences of ventilating tubes

• short general anaesthesia
• open middle ear
• atrophy and atelectasis of tympanic membrane
• surgical complications

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• Negative Prognostic factors
• Passive smoking
• Younger children at onset of OME
• Craniofacial malformations, Down syndrome
• Day-care attendance

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Otitis media

• klinische directe en indirecte
  antibioticum
• gevolgen kosten resistentie
• PREVENTIE

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Preventie OMA

• Beïnvloeden risicofactoren
• Chirurgie
• Chemoprofylaxie
• Immunoprofylaxie

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1. Beïnvloeden risicofactoren

• Gastheer afwijkingen KNO-gebied
  immunologische afwijkingen
• Omgeving dagverblijf
• passief roken
• fopspeen
• borstvoeding beschermt

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2. Chemoprofylaxie

• Meta-analyse (9 studies)
• Antibioticum profylaxie 0.11 episodes
  OMA / maand
• Williams et
  al. JAMA 1993

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Grafiek profylaxis
Antibioticaprofylaxie
Brook CID 1996
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3. Immuunprofylaxie

• Microbiologie
• Passieve immuunprofylaxie (immuunglobuline)
• Actieve immuunprofylaxie
• (vaccinatie)

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3.1. Passieve immuunprofylaxie

• Gammaglobuline IV - OM model in chinchillas
• (Shurin et al. 1988)
• - kinderen met rec. OMA
• (Shurin et al.1993)
• RSV IG IV - reduce incidence and severity of
  RSV lower respiratory tract
  infections
• (Simoes et al. 1996)

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3.2.Actieve immuunprofylaxie (vaccinatie)

• Influenza A virus vaccin
• Finland
• Kinderen 1-3 jaar
• Follow-up 6 weken
• Aan influenza A virus gerelateerd aantal OMA 86
• Totaal aantal OMA (in influenzae seizoen) 36
• Heikinen et al. Am J Dis Child 1991

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Pneumococcen vaccins

• Pneumococcen polysaccharide vaccin
• ( Pneumovax / Pneumune)
• Pneumococcen conjugaatvaccin
• ( Prevenar)

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Vaccine efficacy on AOM prevention
Belgian OMAVAX trial
Dutch OMAVAX trial
PCV/PSV
Control
Control
Cumulative hazard
Cumulative hazard
n 78 RR (95 CI) 1,16 (0,69 1,96)
n 383 RR (95 CI) 1,29 (1,02 1,62)
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Time after complete vaccination
Time after complete vaccination
Veenhoven et al, abstract ISPPD, 2002
Dhooge Van Kempen, 2002
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