Chapter 6 Surgery of Ventilation and Mucosal Disease
Bilateral myringotomy with placement of ventilation tubes is the most common surgical procedure performed in the United States. An estimated 1.05 million tympanostomy tube procedures are performed annually in the United States.1 In addition, otitis media is the most common diagnosis of patients who make office visits to physicians in the United States—the diagnosis increased from about 10 million visits in 1975 to 25 million in 1990.2 The annual visit rate for children younger than 2 years statistically increased by 224% during one study period.3 Otitis media with effusion (OME) incurs approximately $5 billion annually in direct and indirect costs.1 Because of the magnitude of the disease and its impact on society, and conflicting reports over the most appropriate and cost-effective management of the problem,1,3–5 consensus on the treatment of OME has been difficult to achieve. Attempts have been made to devise an algorithm for the management of OME in young children,6 and these guidelines have been recently reviewed and updated (see later).7,8 This chapter reviews the terminology, epidemiology, pathophysiology, and medical and surgical treatment of OME.
TERMINOLOGY
Acute Otitis Media without Effusion
Acute otitis media (AOM) without effusion is characterized by an inflamed middle ear mucosa and tympanic membrane in the absence of an effusion; this can be seen in the early stages of AOM or during its resolution. The tympanic membrane appears dull, erythematous, hypervascular, and inflamed; normal landmarks are often lost. In infants and children, AOM without effusion is usually caused by the same organisms that are isolated from acute OME.9 Treatment principles are the same and are discussed later.
Acute Otitis Media with Effusion
Acute OME occurs most frequently in infants. Redness with or without bulging of the tympanic membrane, fever, irritability, and pain are the hallmark signs and symptoms. An older child with acute OME has a red tympanic membrane and middle ear effusion, but may not have pain or fever. The middle ear effusion is generally purulent. Casselbrant and associates10 reported a cumulative incidence of acute OME of 43% in a study of 198 newborns followed monthly until the age of 2 years. In the Greater Boston Otitis Media Study Group, infants had an average of 1.2 and 1.1 episodes per year, with 46% of children having had 3 or more episodes by the age of 3 years.11
Otitis Media with Effusion
Otitis media with effusion simply refers to fluid in the middle ear without signs or symptoms of ear infection. Asymptomatic OME can be classified as acute (<3 weeks), subacute (3 weeks to 3 months), or chronic (>3 months).12 Acute and chronic refer to the temporal course of the disease, not to severity. Synonyms of OME include secretory otitis media, nonsuppurative otitis media, or serous otitis media; the most commonly used term is OME.
Chronic Suppurative Otitis Media
Chronic suppurative otitis media (CSOM) is a stage of ear disease in which there is chronic infection of the middle ear and mastoid, and in which a central perforation of the tympanic membrane (or a patent tympanostomy tube) and discharge (otorrhea) are present.13 To meet the requirement for “chronic,” the otorrhea should be present for 6 weeks or longer. The infection involves the mastoid and the middle ear, and usually drains through a central perforation. Chronic otorrhea through a nonintact tympanic membrane (perforation or ventilation tube) may or may not be accompanied by cholesteatoma. Cholesteatoma may or may not result in CSOM. CSOM should not be confused with chronic OME; in the latter, no perforation is present, and the fluid is not purulent.
EPIDEMIOLOGY
Teele and colleagues11,14,15 found that 13% of children in their study groups had at least one episode of AOM by age 3 months; that percentage increased to 67% by 12 months. By age 3 years, 46% of children had three or more episodes of AOM. The highest incidence of AOM was found in children 6 to 11 months old. Most children with multiple recurrences of otitis media have their first episode before age 12 months.
An episode of AOM is a significant risk factor for the development of OME. Many investigators have documented persistent middle ear effusion after a single episode of AOM.14–17 Middle ear effusion has been shown to persist after an episode of AOM for 1 month in 40% of children, 2 months in 20%, and 3 or more months in 10%.15
Risk Factors
Risk factors for OME include male gender, recent upper respiratory infection, allergic rhinitis, first-degree relative with allergy, bottle feeding, cigarette smoke in the house, increased number of siblings in the house, and, probably the most important, daycare.18 Children in a public daycare facility have a fivefold increase in otitis media at age 2 years compared with children in home care.19 Whites and Hispanics are more susceptible than African Americans; Native Americans and Inuit are at even greater risk.
Microbiology
Bluestone and coworkers20 obtained aspirates of middle ear effusions by tympanocentesis in infants and children with AOM or OME. Of aspirates from ears with AOM, 35% grew Streptococcus pneumoniae, 23% grew Haemophilus influenzae, and 14% grew Moraxella catarrhalis.20 S. pneumoniae remains the most common bacterium causing AOM.21–23 Introduction of the pneumococcal vaccine may significantly reduce the incidence of pneumococcal disease, including otitis media.24–26
Asymptomatic middle ear effusion (OME) had been previously thought to be sterile. Newer, more sensitive cultures and the introduction of polymerase chain reaction (PCR) testing have shown bacteria and bacterial DNA in asymptomatic middle ear effusions.27 These investigators found that 77% of middle ear effusions had evidence of the three major organisms by PCR (with or without being culture positive), whereas only 28% were culture positive. The most common bacteria were H. influenzae (54.5%), M. catarrhalis (46.4%), and S. pneumoniae (29.9%).27 By comparison, in an earlier study of ears with OME, 30% of aspirates did not grow bacteria, 45% grew “other” strains, 15% had H. influenzae, 10% had M. catarrhalis, and 7% grew S. pneumoniae.20 Other bacteria include Staphylococcus aureus and gram-negative enteric bacilli. In infants younger than 6 weeks, gram-negative bacilli cause about 20% of AOM episodes.21
The bacteriology of CSOM with or without cholesteatoma is different. Most frequently isolated bacteria include Pseudomonas aeruginosa (most common), S. aureus, Corynebacterium, Klebsiella pneumoniae, and anaerobes.23 With better culture techniques, anaerobes have been increasingly isolated from chronic suppurating ears; these organisms include Bacteroides spp., Peptococcus spp., Peptostreptococcus spp., and Propionibacterium acnes.23
PATHOPHYSIOLOGY
Acute Otitis Media
AOM is principally a sequela of a viral upper respiratory infection. The upper respiratory infection impairs ciliary motility and breaks down mucosal barriers that prevent bacterial adherence and growth. Poor clearance of secretions results in stasis and allows bacteria to infect the host. Pathogenic bacteria that appear in the nasopharynx after an upper respiratory infection are the same as the bacteria cultured from middle ear effusions (S. pneumoniae and H. influenzae).28 The adenoid seems to be the source of infecting bacteria in middle ear disease; Pillsbury and associates29 showed higher bacterial colony counts in the adenoids of children with recurrent otitis media than in children undergoing adenoidectomy for adenoid hypertrophy without otitis media. During an upper respiratory infection, sneezing, blowing the nose, and swallowing in the presence of nasal obstruction may create a pressure differential between the nasopharynx and middle ear, forcing bacteria through the Eustachian tube into the middle ear.
Chronic Otitis Media with Effusion
Two theories have been proposed to account for the persistence of middle ear effusion in the absence of acute infection. As shown by the Boston Collaborative Group, persistent effusion is a natural sequela of acute middle ear infection.15 Effusion persists for 1 month in 40% of children after an episode of AOM, 2 months in 20%, and 3 or more months in 10%.15 Because pathogenic bacteria and bacterial DNA have been recovered from “nonacutely infected” fluid in the middle ear,21,27,30–31 it seems that Eustachian tube obstruction and retained secretions in these cases are the result of the acute infection, rather than the cause.
Eustachian tube dysfunction may be a primary disorder that causes acute and chronic OME. Primary Eustachian tube dysfunction results in underaeration and poor ventilation of the middle ear space; this leads to negative pressure in the middle ear with resultant transudation of fluid. Negative middle ear pressure also causes hypoxia and hypercapnia of the middle ear mucosa, resulting in goblet cell hyperplasia and hypersecretion.32,33 The result is a sterile fluid that becomes secondarily infected. The fluid resolves only after adequate ventilation is restored, either by return of Eustachian tube function or by placement of alternative ventilation, such as a ventilation tube.
According to Gates,34 the available evidence lends support to the theory that the secretory changes in the middle ear that exist in cases of chronic OME are the histologic sequelae of chronic infection, rather than a separate pathologic disorder. Most cases of chronic OME begin as acute infection of the middle ear; postinflammatory alterations in the mucosa of the middle ear and Eustachian tube lead to persistent effusion. Obstruction of the Eustachian tube is secondary to the infection and not the cause of it. Eustachian tube obstruction prevents clearance of secretions, impedes ventilation and drainage, and perpetuates the inflammatory process.
Allergic rhinitis has been recognized as a risk factor in the development of chronic OME. The actual prevalence of “allergic” chronic OME has been reported in the literature with a very broad range of 10% to 90%.32
Although it is beyond the scope of this chapter to provide extensive details of the type I hypersensitivity response, we provide a short summary. Atopic disease is initially characterized by antigen exposure and specific sensitization. Subsequent re-exposure results in mast cell degranulation and the release of numerous inflammatory mediators, including histamine, cysteinyl leukotrienes, and cytokines, and the infiltration of eosinophils, mast cells, basophils, and other inflammatory cells.35 These cells further the release of histamine and cysteinyl leukotrienes, resulting in increased mucosal blood flow, vascular permeability, and mucus production, and continued recruitment of inflammatory cells.
As in the nose, continued allergic inflammation in the middle ear is associated with a marked increase in the number of mucosal mast cells and cell bound IgE.36 In addition to degranulation, mast cells may also pre-sent antigen to B lymphocytes, dendritic cells, and monocytes, resulting in the further release of proinflammatory36 cytokines, including tumor necrosis factor, interleukin (IL)-1, and IL-6.36 IL-4 is released by activated mast cells and circulating basophils, and naïve T cells. IL-4 eventually mediates an isotypic switch from a predominantly TH1 lymphocytic profile of naïve T cells to the proinflammatory TH2 cells that are the hallmark of atopic disease. The further release of IL-5, IL-9, and IL-13 by TH2 lymphocytes results in the recruitment and activation of more basophils, mast cells, and eosinophils, insuring the development of a chronic allergic milieu.33
Nose
The nose is the target organ most commonly involved in the allergic reaction, and numerous publications have supported the concept that allergic inflammation resulting in nasal congestion may result in significant Eustachian tube obstruction.37–40 The sensitized mucosa of the nose, adenoid bed, or nasopharynx exposed to allergens releases cytokines, resulting in increased mucus secretion, edema, and inflammation around the torus tubarius. The resulting Eustachian tube obstruction has a negative effect on middle ear ventilation, resulting in the production of chronic OME.
Middle Ear Space
Although it is intuitively tempting to consider the middle ear the most likely target organ of an allergic reaction resulting in the production of chronic OME, there is likely little antigen exposure to the middle ear mucosa. The Eustachian tube is normally closed, unless one is swallowing or yawning, which would make it much less likely than the nose to allow physical contact with inhaled aeroallergens. Supporting this limited role, Bernstein39 suggested, based on a study determining the local production of IgE in middle ear mucosal biopsy specimens of atopic children undergoing pressure equalization tube insertion, that the middle ear mucosa likely serves as the target organ of an allergic reaction less than 10% of the time. Other authors disagree, however. Eustachian tube dysfunction has been reported from transtympanic challenge on antigen in sensitized animals.41,42 Ebert and colleagues43 showed a similar finding with intratympanic histamine mast cells found to be present in the middle ear effusions and biopsy specimens of children with chronic OME, suggesting local inflammation and reaction.44–47
Eustachian Tube
Several mechanisms for Eustachian tube dysfunction have been proposed. First, congestion of the nasal mucosa may produce a retrograde spread of edema and Eustachian tube dysfunction. Second, poor mucociliary function, either innate or resulting from allergic or other inflammatory etiologies, may lead to retention of secretions resulting in obstruction of the Eustachian tube.48,49 Third, inhalation of aeroallergens with subsequent direct allergic inflammation within the Eustachian tube may produce venous engorgement and hypersecretion of mucus, with the subsequent obstruction affecting gas exchange in the middle ear space.50 The resulting negative pressure allows a transudation of fluids into the middle ear space by the interruption of cellular tight junctions.39,50 Later, persistent obstruction of the Eustachian tube with mucus results in chronic middle ear inflammation, with resulting mucosal metaplasia and increased glandular activities of goblet cells.39,50
Increasingly, physicians who treat allergic patients embrace the concept of one airway, whereby the inflammatory response in one portion of the airway may also lead to inflammatory changes in other portions. The classic example is the recognition of the intimate relationship existing between the upper and lower airways. In a study of atopic subjects, inhaled allergen challenge isolated to the nose produced inflammatory changes in the upper and lower airways. These changes included increased adhesion molecules, increased bronchial hyperreactivity, and eosinophil infiltration.51 Although it is important that we continue research to define the immunology involved in the subset of patients with chronic OME who have allergy as an underlying etiology, we should keep in mind that allergy does affect the common airway, and that lessening significant allergic inflammation in the entire anatomic area would be beneficial.
TREATMENT AND PATIENT SELECTION
Acute Otitis Media and Recurrent Acute Otitis Media
For a single episode of AOM, antimicrobial therapy targets the most common offending pathogens: S. pneumoniae, H. influenzae, and M. catarrhalis. We recommend a 10-day course of amoxicillin as first-line empirical therapy. Clinical practice guidelines from the Agency for Healthcare Research and Quality (AHRQ) argue for observation without antibiotic therapy in selected patients with AOM (Table 6-1).7 Studies have shown an increase in the β-lactamase-producing organisms, H. influenzae and M. catarrhalis.19,52 β-Lactamase renders the organism that produces it resistant to penicillin (and ampicillin). Persistent or recurrent AOM may be secondary to a β-lactamase-producing organism and requires a broader spectrum antibiotic53; good choices in this setting include cefuroxime, erythromycin-sulfisoxazole, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and cefaclor. Antipyretics (but not aspirin) are also indicated for children with AOM.
TABLE 6-1 Criteria for Initial Antibacterial Agent Treatment or Observation in Children with Acute Otitis Media
| Age | Certain Diagnosis | Uncertain Diagnosis |
|---|---|---|
| <6 mo | Antibacterial therapy | Antibacterial therapy |
| 6 mo–2 yr | Antibacterial therapy | Antibacterial therapy if severe illness; observation option if nonsevere illness |
| ≥2 yr | Antibacterial therapy if severe illness; observation option if nonsevere illness | Observation option |
From American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media: Diagnosis and management of acute otitis media. Pediatrics 113:1451-1465, 2004.
A child (or adult) with an infectious complication of otitis media requires more aggressive therapy, including intravenous antibiotics and possible surgical intervention. This subject is beyond the scope of this chapter and is discussed in Chapter 19.
Placement of tympanostomy tubes is effective treatment in the prevention of recurrent otitis media. Many authorities accept four episodes of AOM in 6 months as a criterion for tympanostomy tube placement. Gebhart54 was the first to show a reduction in the number of new episodes of AOM after insertion of tympanostomy tubes.
The role of adenoidectomy in the treatment of recurrent AOM is controversial. Although Paradise and coworkers55 found a significant reduction (28% and 35%) in the incidence of AOM in the first and second years after adenoidectomy, a formal study examining the role of adenoidectomy in the treatment of recurrent AOM has not been done. Results of studies of chronic OME and adenoidectomy may or may not be applicable for patients with recurrent AOM. For patients with recurrent AOM and persistent effusion, adenoidectomy is an appropriate surgical treatment (see the following section on chronic OME).
Chronic Otitis Media with Effusion
As mentioned, 10% of children with AOM have persistent middle ear effusion 3 or more months after resolution of the acute infection.15 Most children clear their effusion within 1 to 2 months; these patients need no further therapy. The few patients who retain fluid in the middle ear longer than 3 months are at risk for other sequelae, including hearing loss, language delay, vertigo or imbalance, tympanic membrane changes (including atelectasis or retraction pockets or both), further middle ear pathology (including ossicular problems and adhesive otitis), and discomfort with nighttime wakefulness and irritability.
Numerous treatment strategies have been proposed for chronic OME: antimicrobial therapy, antihistamines/decongestants, corticosteroids, tympanostomy tubes with or without adenoidectomy, and mastoidectomy. Updated clinical practice guidelines from the AHRQ do not recommend antibiotics, antihistamines, decongestants, or corticosteroids for the treatment of chronic OME.8 These modalities and allergic strategies are now reviewed.
Antimicrobial Therapy
More sensitive techniques (e.g., PCR) have shown bacterial DNA in middle ear effusions previously thought to be “sterile” or culture negative. Prolonged antibiotic therapy theoretically eradicates the organism and eliminates the chronic source of effusion. Some studies have shown the efficacy of antibiotics in OME.21,56 Despite these studies, theoretical and practical arguments can be made against their use in chronic OME. Clinical experience indicates that the utility of antibiotics is reduced as the number of treatment courses increases. Children receiving four or more courses of antibiotics over a 3 to 4 month period are most likely not going to resolve their effusion with medical management. Other adverse effects of prolonged antimicrobial therapy include development of anaphylaxis and allergic reactions; hematologic disorders; and the emergence of resistant organisms, a serious worldwide problem best shown by the development of resistance to penicillin by S. pneumoniae. Finally, Rosenfeld and Post found through a large meta-analysis of existing studies that the benefit of antimicrobial therapy in chronic OME is slight.
Antihistamines and Decongestant Therapy
Oral antihistamine and decongestant combinations and monotherapy have not been shown to be beneficial in the treatment of chronic OME.56 The AHRQ clinical practice guideline does not recommend these agents for chronic OME.8 A possible exception may be in an adult patient with allergen-induced Eustachian tube dysfunction. Stillwagon and colleagues57 investigated the effects of pharmacotherapy on allergen-induced Eustachian tube dysfunction. In this study, adults with a history of seasonal allergic rhinitis to ragweed pollen received either a combination of antihistamine and decongestants or placebo for 7 days followed by an intranasal challenge with ragweed pollen. Eustachian tube obstruction occurred in fewer patients receiving active treatment than in patients receiving placebo. They concluded that pre-exposure treatment with antihistamines in patients with allergic rhinitis may help decrease the risk of developing Eustachian tube dysfunction. There are no studies to date on a possible role of intranasal antihistamines on treatment of middle ear effusion.
Antileukotrienes
Antileukotrienes have not been well studied for a possible role in the treatment of chronic OME. Combs58 found a significant decrease, however, in the duration of middle ear effusion in otitis-prone children treated with montelukast after AOM compared with a control group. The reader is advised to take into account the paucity of research and the expense of this relatively safe medication when debating its possible merit in treatment.
Corticosteroid Therapy
Steroid therapy for chronic OME has been controversial. Lambert59 found no difference in outcomes between the steroid group and the control group with chronic OME. At this time, the AHRQ guideline does not recommend steroid therapy for chronic OME.8
Treatment for Food Allergy
The younger the child with suspected allergies, the more likely the antigen will be ingested rather than inhaled. Juntti and associates60 found that 34% of children with allergic rhinitis or asthma who also had cow’s milk allergy had recurrent OME compared with 13% of children who had allergic rhinitis and no diagnosed milk allergy.
