AIRWAY DISORDERS: CONCEPTS IN MANAGEMENT
| THE ROLE OF EOSINOPHILS IN CHRONIC SINUSITIS —Stilianos K. Kountakis, MD, PhD, Professor and Vice
Chairman, Director of Rhinology and Residency Program, Department of Otolaryngology—Head and Neck Surgery, Medical
College of Georgia, Augusta
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| Allergies: second most common cause of acute sinusitis; fuel inflammation associated with chronic sinusitis;
sensitization—initial phase of allergic reaction; begins when macrophage metabolizes allergen; interaction between
HLA class II complex and T-cell receptor; activation of T cells leads to secretion of IgE antibodies specific to sensitizing
antigen; IgE antibodies enter bloodstream and bind to mast cells; early phase of allergic reaction—occurs within minutes
of exposure to sensitizing antigen; previously sensitized mast cells degranulate and secrete preformed inflammatory
mediators that work on blood vessels, nerves, and glands to produce symptoms; neosynthesis of inflammatory mediators
(eg, leukotrienes, prostaglandins) also contributes to symptomatology; late phase of allergic reaction—starts 3 to 4 hr
after re-exposure to allergen; lasts 4 to 24 hr; occurs in ≤50% of allergic individuals; develops when inflammatory mediators
serving as chemotactic factors attract additional inflammatory cells (including eosinophils) to area of exposure;
point—patients with chronic sinusitis and allergies require aggressive treatment to improve symptoms
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| Superantigen: present in some individuals; usually toxin produced by bacteria; bypasses complex genetically-mediated
safety mechanisms; requires only 2 domains (instead of 5) to initiate allergic reaction; elicits powerful stimulation of T-
cell pathway, with recruitment of eosinophils and formation of extensive aggressive respiratory epithelial inflammation
and polyps; nasal polyps with yellow coating—recur following initial excision and aggressive steroid therapy; may be
related to superantigen phenomenon; combining surgery, sinus drainage, and ≥6 mo of nebulized antibiotics may facilitate
management
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| Nasal polyposis: pathogenesis complex; insults such as altered anatomy, viral or bacterial infection, or allergies lead to
upregulation of nasal epithelium and recruitment of inflammatory cells; eosinophils—mediate positive feedback mechanism
necessary for polyp formation; secrete toxic substances that can damage nasal epithelium; also secrete cytokines
and interleukins that recruit more eosinophils to nasal epithelium; subsequent positive upregulation of inflammation continues
and contributes to growth of polyps; polyps—expand and enlarge in presence of marked edema (watery portion of
polyp responds to steroid therapy); become more steroid-resistant with age and deposition of fibrin, and eventually require
surgical removal
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| Eosinophils: antiparasitic cells in respiratory epithelium; produce leukotrienes that cause increased vascular permeability;
recruit leukocytes; secrete toxic substances
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 | Chronic rhinosinusitis as end result of immune system response to fungal infection (Ponikau theory): concept—
eosinophils secrete major basic protein that kills fungi and damages mucosal epithelium; as bacteria enter damaged
mucosa, inflammatory cells migrate to site of infection; chronic sinusitis and inflammation of nasal epithelium develop
in response to production of inflammatory mediators; problem—theory does not explain why only certain individuals
with nasal fungi develop chronic sinusitis
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| Classification of sinus disease severity: standardized means of studying pathology; prompted pathologists to provide
physician with information necessary to prevent recurrence; group I (polyps with sinus tissue eosinophilia)—
most severe and difficult-to-treat type of rhinosinusitis; asthma, polyps, and Samter’s triad may be present; evaluation of
polyp and mucosal tissue shows eosinophil concentrations ≥5 per high power field; aggressive treatment with anti-inflammatory
medication prevents recurrence; group II (polyps without sinus tissue eosinophilia)—polyps associated
with risk for recurrence; absence of eosinophilia produces milder form of rhinosinusitis; group III (sinus tissue eosinophilia
without polyps)—patients considered “time bombs” that can progress to group I disease; group IV (absence of
eosinophilia and polyps)—easiest group to manage; once obstruction removed surgically, subsequent problems can be
treated medically
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| MAINTAINING DISEASE CONTROL IN ASTHMA —Kaiser G. Lim, MD, Assistant Professor of Medicine, Mayo
Clinic College of Medicine, Rochester, MN
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| Asthma severity: implies intensity of disease process; measured by variety of means, eg, medication use, lung function,
time in intensive care unit (ICU)
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| Asthma control: focuses on how disease manifestations minimized—patient appropriately managed for severe
asthma may be asymptomatic; patient improperly managed for mild asthma may be incapacitated by disease; manifestations
of concern to patient—awakening at night; shortness of breath; normal lifestyle (normal exercise capacity); frequency
of visits to emergency department; test for asthma control—5-question test routinely used; good scores (>19)
correlate with quality of life and degree of health care utilization
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| Gaining Optimum Asthma ControL (GOAL) study data suggest: possible to use asthma control as treatment
end point; step-up therapy may delay asthma control; corticosteroid-naïve patients probably do not require combination
of inhaled corticosteroid (ICS) and long-acting bronchodilator; some individuals may require >500-µg dose of steroid,
eg, data show >50% of subjects required 1 g of fluticasone
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| Points to ponder: increasing ICS dose does not always achieve linear response in controlling exacerbations; leukotriene
receptor antagonists—useful add-on therapy; montelukast (Singulair) possesses some anti-inflammatory properties;
patient response determines whether long-acting bronchodilator or leukotriene receptor antagonist drug of choice
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| Asthma action plan: management approach can be inadequate for helping patient cope with asthma, eg, while 65% of
patients studied underwent allergy testing, only 3.6% received formal education in achieving environmental control
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| Controlling exacerbations: clinical data show—side effects of steroid therapy can be avoided by administering moderate
doses of prednisone, ie, 30 mg/day or 0.5 mg/kg per day for 10 days; approach achieved rapid improvement in ≤2
days; extend prednisone therapy for additional 10 days and maintain ICS therapy—if patient’s peak flow does not
reach 80% of normal at 5 days and symptoms persist; data show doubling dose of ICS did not affect disease course;
fluticasone option—some data suggest 2 mg of fluticasone equaled efficacy of 14 mg of prednisone; when compared
to fluticasone, prednisone burst proved equally effective, less expensive, and easier for patient to remember to administer
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| Additional aspects: patients with frequent exacerbations—key factors contributing to problem include chronic sinusitis,
obstructive sleep apnea, reflux, and recurrent respiratory symptoms; psychogenic problems and chronic sinusitis
considered key independent factors; key factors that can prevent asthma exacerbations include—ICS; combination
of ICS and long-acting bronchodilators in properly selected patients; leukotriene receptor antagonists as add-on therapy
(less effective than bronchodilators); anti-IgE therapy in patient with allergic background; bottom line—ICS
most effective monotherapy
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| PEDIATRIC SEPTOPLASTY —John Bent, MD, Assistant Professor, Albert Einstein College of Medicine of Yeshiva
University, New York, NY
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| Nasal obstruction: pediatric nasal septal deviation (NSD)—frequently mild; not primary cause of nasal obstruction;
septoplasty not recommended for managing asymptomatic deviation early in childhood; differential diagnosis—allergic,
chronic, or vasomotor rhinitis; chronic sinusitis; tonsillar and/or adenoidal hypertrophy
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| Pediatric septoplasty: open septoplasty—use limited by concern over gross nasal growth disturbances; Crysdale approach
to open septorhinoplasty considered effective (children undergoing Crysdale approach developed clinically insignificant
differences in dorsal nasal length and tip protrusion); point—additional data verify safety of open and intranasal
excisions
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| Clinical scenarios: teenage boy collides with pole and sustains left anterior septal deviation—rule out septal hematoma;
closed reduction generally effective for repairing injury (mucoperichondrial flap rarely necessary to reposition
septum; in young children, reduction should take place within 2-4 days); congenital NSD—symptomatic patients become
worse if untreated; with anterior deviation, expose medial crura of lower lateral cartilages (repair carried out via sublabial
or open surgery; intranasal approach more difficult); open septorhinoplasty or septoplasty preferred for
repositioning cartilage between medial crura; adolescents—managed as adults (in general, nose almost fully grown by
15-21 yr of age); computed tomography (CT) useful when coexisting pathology may affect repair
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| Conclusions: in children, NSD usually—asymptomatic; does not require repair; untreated symptomatic pediatric
NSD—does not improve and may worsen with time; assess risk potential when planning management; points—repair
symptomatic, congenital, and acute deviations; anterior deviations do well with open repair
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| CULTURES IN OFFICE PRACTICE: RHINOSINUSITIS —Andrew H. Murr, MD, Professor of Clinical Otolaryngology,
Vice-Chair, Department of Otolaryngology, University of California, San Francisco, School of Medicine
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| Culture evaluation: may help determine disease etiology as well as identify pathogen and hone treatment selection
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| Etiologic factors: common cold—causes sinusitis and rhinitis; specific viruses include rhinovirus, coronavirus, respiratory
syncytial virus (RSV), and adenovirus; inflammatory disease—multiple potential causes; larger than bacterial
category of disease etiology
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| Acute bacterial rhinosinusitis: antibiotic therapy can be directed toward prevalent pathogens—Streptococcus pneumoniae
and Haemophilus influenzae in adults; Moraxella catarrhalis in children; factors creating predisposition
to bacterial rhinosinusitis—viral upper respiratory tract infection (URI); allergic rhinitis producing mucus stasis; anatomic
obstruction; air pollution; nasal polyps; additional concerns—overgrowth of endotoxin-producing staphylococci
or other bacteria in static secretions; medication-induced metaplastic change in ciliated respiratory epithelium;
anaerobic infection from dental disease
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| Defining disease: manifestations of current time-centered approach to managing sinusitis—12-wk rule for determining
treatment failure (based on old definition); tendency to focus on time, not etiology, as basis for defining disease
(ie, acute sinusitis lasting ≤4 wk, subacute sinusitis lasting 4 to 12 wk, and recurrent, acute sinusitis defined by number
of disease episodes); risk for progression of bacterial rhinosinusitis—key concern; patients can progress from mild
to moderate disease; complicated cases can involve epidural or subdural abscesses, meningitis, cavernous sinus thrombosis,
and brain abscess
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| Chronic rhinosinusitis with or without nasal polyps: may provide better basis for clinical evaluation and classification;
when nasal polyps present—problem usually visualized with endoscopy; CT can detect evidence of disease; inflammatory
disease process may be one of several etiologic factors; patient with bacterial rhinosinusitis probably has—
history of antecedent URI; pus visible on endoscopy
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| Factors underscoring importance of culture analysis: new problems associated with common infectious
organisms—fungi (eosinophil-mediated rhinosinusitis and allergic fungal sinusitis [AFS]); Staphylococcus aureus
(endotoxin production or biofilm concept); Pseudomonas (lifelong history of chronic rhinosinusitis associated with
cystic fibrosis [CF])
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| Drug resistance: major concern, eg, some strains of S pneumoniae losing susceptibility to penicillin, trimethoprim-sulfamethoxazole
(Bactrim), and some macrolides; “shotgun' treatment can train some bacteria to become resistant to antibiotic
therapy, eg, only 20% of S pneumoniae strains remain susceptible to cefaclor (Ceclor); culture analysis
can—document drug susceptibilities of specific organisms; aid selection of more effective antibiotics in patients refractory
to initial therapy
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| Additional aspects: time course of sinusitis—viral infection during early disease phase; aerobic infection subsequent to
viral infection; as infection persists, resistant organisms, anaerobes, and fungi become involved; once surgery
performed—spectrum of bacteriology changes to include organisms rarely encountered without surgery, ie,
Pseudomonas, Klebsiella, and Enterobacter; classification according to presence of eosinophils or
neutrophils—neutrophil group considered more standard infectious category
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| Cultures can be used to: ensure optimal antibiotic coverage in patients with acute rhinosinusitis; facilitate selection of
more appropriate antibiotic coverage in patients with chronic rhinosinusitis; detect unusual organisms in patients with continuous
postoperative infection; select appropriate management in immunocompromised patients; facilitate initiation of
broad-spectrum treatment for individuals with complicated rhinosinusitis
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| New tools for culture analysis and determination of pathophysiology of underlying disease: polymerase
chain reaction (PCR) analysis of fungus obtained via dental-brush swab of middle meatus—analysis
showed 40% of diseased patients and 40% of disease-free patients had fungus; cohort with fungi may be more likely to
have eosinophil-related rhinosinusitis (large β-error may be involved in making determination); calcium alginate (Calgiswab)
analysis of pus in middle meatus can—determine strain of Staphylococcus involved in infection and help
eliminate associated staphylococcal toxins or biofilm; direct proper therapy against resistant organisms; prompt physician
to perform CF evaluation in patient with Pseudomonas infection; administer appropriate antibiotic therapy for unusual
infecting organism in patient who has undergone revision surgery
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Educational Objectives
| The goal of this program is to educate the listener about current concepts in management of airway disease. After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Assess the role of eosinophils in chronic rhinosinusitis.
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| 2. Review a new system for classifying sinus severity and evaluating pathology.
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| 3. Determine the importance of gaining and maintaining asthma control.
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| 4. Initiate appropriate pediatric septoplasty.
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| 5. Evaluate the clinical significance of culture analysis in otolaryngologic office practice.
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Discussed on This Program
Beclomethasone dipropionate (several trade names)
Budesonide [Entocort EC, Pulmicort Respules, Pulmicort Turbuhaler, Rhinocort, Rhinocort Aqua]
Cefaclor [Ceclor, Ceclor CD, Ceclor Pulvules]
Cocaine [Cocaine HCl, Cocaine Viscous]
Fluticasone propionate [Cutivate, Flovent, Flovent HFA, Flovent Diskus, Flovent Rotadisk, Flonase]
Montelukast sodium [Singulair]
Penicillin (several trade names and preparations]
Prednisone (several trade names and preparations)
Trimethoprim-sulfamethoxazole (co-trimoxazole; TMP-SMZ) [Bactrim, others]
Suggested Reading
Kips JC et al: A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-
dose budesonide in asthma. Am J. Respir Crit Care Med 161:996, 2000; Klossek JM et al: Bacteriology of chronic purulent
secretions in chronic rhinosinusitis. J Laryngol Otol 112:1162, 1998; Konstantinidis I et al: Long term results
following nasal septal surgery. Focus on patients’ satisfaction. Auris Nasus Larynx 32:369, 2005; Lim KG: Management
of persistent symptoms in patients with asthma. Mayo Clin Proc 77:1333, 2002; O’Byrne PM: Pharmacologic interventions
to reduce the risk of asthma. Proc Am Thorac Soc 1:105, 2004; Ponikau JU et al: Striking deposition of toxic
eosinophil major basic protein in mucus: implications for chronic rhinosinusitis. J Allergy Clin Immunol 116:362, 2005;
Ragab A et al: Fungal cultures of different parts of the upper and lower airways in chronic rhinosinusitis. Rhinology
44:19, 2006; Sin DD et al: Pharmacological management to reduce exacerbations in adults with asthma: a systematic review
and meta-analysis. JAMA 292:367, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Bent gave his scientific presentation at New York Rhinology Update held April 21 to 23, 2006, in New York City by the
New York University Post-Graduate Medical School and Albert Einstein College of Medicine; Dr. Kountakis gave his scientific
presentation at the Third Annual Porubsky Symposium held June 10-11, 2005, in Augusta, GA, and sponsored by the
Medical College of Georgia; Dr. Lim gave his scientific presentation at Allergy and Clinical Immunology: 64th Annual
Course, held April 7, 2006, in Minneapolis, MN, and sponsored by the University of Minnesota Medical School; Dr. Murr
gave his scientific presentation at University of California, San Francisco, School of Medicine’s Advanced Endoscopic
Sinus Surgery Dissection Course held April 27-29, 2006, in San Francisco. The Audio-Digest Foundation thanks the speakers
and the sponsors for their cooperation in the production of this program.
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