Nasal Polyposis: What Every Chest Physician Needs To Know

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Nasal Polyposis: What Every Chest Physician Needs To Know

By M. Szema, MD, FCCP; and C. Monte, MD

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Objectives

Learn how to diagnose and treat nasal polyps.

Understand the background historical issues associated with nasal

polyps.

Learn about the epidemiology of nasal polyps.

Be familiar with comorbid conditions and clinical symptoms.

Understand the histology, putative pathogenesis, and grading system

for nasal polyps.

Key words

allergy; nasal polyposis; polyp; sinus surgery; steroids

Abbreviations

AFS = allergic fungal sinusitis; CF = cystic fibrosis; COX-2 =

cyclooxygenase-2; NSAID = nonsteroidal anti-inflammatory drug;

Nasal polyps are nasal epithelial outpouchings incited by

inflammation.1 Nasal polyposis, a disease of the upper respiratory

tract, can lead to symptoms of a perceived inability to breathe

secondary to nasal obstruction— " stuffiness. " The presence of nasal

polyps may predispose to recurrent episodes of bacterial sinusitis.2

Patients may develop headaches, postnasal drip, facial pain, and

possibly cough.3 Anosmia, hyposmia, and dysgeusia are common. Other

symptoms include rhinorrhea,4 snoring,5 and mouth breathing. Nasal

polyposis may be associated with diseases of the lower respiratory

tract, including asthma,6,7 Kartagener's syndrome,8 and cystic

fibrosis.9 Therefore, a chest physician who improves his or her

clinical acumen regarding nasal polyps will be better able to treat

his or her patients afflicted with this condition.

Historical Background

Nasal polyps were recognized as an illness in Egypt at least 3,000

years ago. Hippocrates developed two surgical methods of nasal

polypectomy in 400 BC: (1) extraction by pulling a sponge through the

nasal passages; and (2) cauterization (loop technique) [Fig 1]. The

former method utilized a round sponge tied with a cord passed through

the loop end of a flexible tin curette. Polyps were removed by

avulsing them through the mouth by pulling these threads. The latter

method, so-called cauterization, involved using powder of black

hellebore—a scarforming, escharotic, caustic substance—for destroying

tissue. Irons were inserted into a syringelike device used as a

protective tube to avoid burning the surrounding tissue.10

of Aegina, in the 7th century, wrote a book chapter

called " About Polyps, " wherein he noted that a polyp " is a tumor

which is created in the nose and which takes its name from the marine

animal (named `polyp') because it resembles the flesh of this

creature and its behavior; as the animal protects itself with its

tentacles, so the polyp reacts and extends itself in the nose of a

sufferer, obstructing the nostrils and provoking dysfunction in

breathing and talking. " He described a polypodic sword (polypus

knife) and polypoxestes (polypus eradicator)

Epidemiology

Nasal polyps occur in all races and social classes. They affect 1 to

2% of the adult population in Europe. The male:female ratio is

between 2:1 and 4:1. A hereditary association has been described.

Symptoms usually manifest after the age of 20 years. Nasal polyposis

is rare in healthy children (0.1% prevalence) but is common in

patients with cystic fibrosis (CF). CF must be excluded in any child

with nasal polyps, even in the absence of overt pulmonary

disease.11,12 Figure 3 shows the CT appearance of polyps.

Comorbid Medical Conditions

Ten disease entities associated with nasal polyps are important to

the chest physician: IgE-mediated disease, asthma, aspirin and

nonsteroidal antiinflammatory drug (NSAID) intolerance, Kartagener's

syndrome, CF, allergic fungal sinusitis (AFS), Churg-Strauss

syndrome, Young's syndrome, nonallergic rhinitis with eosinophilia

syndrome, and sarcoidosis.

IgE-Mediated Disease

The incidence of allergies in patients with nasal polyps, as detected

by allergy skin tests, a measure of specific IgE from epidermal mast

cells, is no higher than that of the general population. However,

some authors suggest that a subgroup of patients with nasal polyps

have IgE-mediated disease with IgE in nasal secretions equivalent to

those patients with allergic rhinitis. It remains to be determined

why some patients develop allergic rhinitis and others may have

superimposed nasal polyposis.13 One study showed that 29.4% of

patients with nasal polyps had allergic rhinitis.12

Asthma

Roughly 70% of patients with nasal polyps have asthma.11,12 Nasal

polyps typically occur 10 years after the diagnosis of asthma.14 The

Rhode Island Hospital allergy group reviewed several thousand records

and noted that 6.7% of their asthmatic patients had nasal

polyposis.15 These authors tested patients for skin-prick reactivity

to " trees, grasses and ragweed pollen extracts, animal danders, and

selected molds. " Of asthmatics with negative skin tests, 12.5% had

nasal polyps, whereas 5% of asthmatics with positive skin tests had

polyps.15 A recent Israeli series of 34 asthmatics with massive nasal

polyps determined that functional endoscopic sinus surgery improved

symptoms of nasal breathing and quality of life, but did not alter

the clinical course of asthma postoperatively.16

Aspirin and NSAID Intolerance

Both aspirin and NSAID intolerance are associated with nasal polyps.

For example, the antiphlogistics indomethacin and ibuprofen are cited

as culprit medications. About 36% of patients with aspirin

intolerance have nasal polyps.17 Although Widal described a triad of

nasal polyps, aspirin intolerance, and asthma in 1922, it was not

until 1967 that Samter and Beer promoted this clinical observation we

now know as Samter's triad. This entity occurs in 36 to 39% of

patients with nasal polyps.18 For those patients with Samter's triad,

desensitization to aspirin helps. Approximately 65% of patients who

receive nasal steroids and aspirin desensitization have improvement

in hypersecretion and nasal blockage, while 74% show shrinkage of

nasal polyps and improvement in symptoms of hyposmia or anosmia.6

Kartagener's Syndrome

This is a rare ciliary dyskinesia syndrome (1/20,000 births) that

involves bronchiectasis, situs inversus, and sinusitis. These

patients may have nasal polyps.7 The original description by

Kartagener noted a mirror-image organ arrangement (situs inversus),

bronchiectasis, and sinusitis. Electron microscopic abnormalities in

sperm tails from infertile men are a result of structural ciliary

abnormalities. A dyskinetic beat pattern of cilia is seen, while 10%

have a beat frequency within the normal range.18a

Cystic Fibrosis

One of the most common hereditary diseases in Caucasians is CF, which

often arises from an autosomal recessive defect of the cystic

fibrosis transmembrane regulator (CFTR) gene on chromosome 7. This

gene codes for a chloride channel on respiratory-tract epithelium.

This defect causes these patients to have thick, inspissated

secretions, which predisposes them to infections in both the lungs

and the sinuses. The classic bacterial culprits are Pseudomonas spp.

CF is also associated with digestive malfunction (pancreatic exocrine

gland dysfunction/meconium ileus).19 In one study, 37% of patients

with CF had nasal polyps.20

Allergic Fungal Sinusitis

Nasal polyposis, crust formation, and sinus cultures growing

Aspergillus were first noted in 1976 by Safirstein,21 who observed

the similarity to allergic bronchopulmonary aspergillosis. There is

currently no consensus regarding the diagnostic criteria for AFS. The

most recently published criteria are from Bent and Kuhn22 in 1994.

These include the presence of (1) Gell and Coombs type I

hypersensitivity (IgE-mediated), (2) nasal polyps, (3) characteristic

radiographic findings on sinus CT and MRI, (4)

eosinophilic " allergic " mucin without fungal tissue invasion, and (5)

positive fungal stain. The characteristic CT findings are serpiginous

areas of increased attenuation within the sinuses.23 Bony erosion

with disease extension is present in approximately 20% of cases.24

The characteristic MRI findings are hypointense regions with

surrounding enhancement on T1-weighted images, as well as decreased

signal intensity with surrounding enhancement on T2-weighted

images.25,26 Grossly, the eosinophilic mucus is rubbery and

tenacious, like peanut butter or axle grease, and can range from

green to brown.22,27 It may be difficult to remove with usual

suctioning.

Histologically, there are sheets of eosinophils, Charcot-Leyden

crystals, and scarce fungal hyphae that will require a silver stain

for identification.22 This eosinophilic mucus is sent for both

pathologic and microbiologic examination, and is very important for

making the diagnosis.28 The mucosa and polyps removed at surgery will

show chronic inflammation, but need to be examined to rule out fungal

tissue invasion.28 The dematiaceous fungi (Bipolaris, Curvularia,

etc.) are the more predominant causative fungi, not Aspergillus.29-31

This condition is most common in the Southwest and Southeast United

States.32 It appears that atopy, as well as specific T-cell human

leukocyte antigen receptor expression, fungal exposure, and abnormal

mucosal immunity, may play a role in its pathogenesis.33

The treatment of choice consists of (1) surgical drainage of the

sinuses, ie, functional endoscopic sinus surgery, to ensure complete

removal of all fungal mucin; followed by (2) immunomodulation in the

form of topical and systemic steroids and/or immunotherapy; and (3)

antifungal medications, either topical or systemic.33

Currently, no guidelines exist as to the optimal steroid regimen

after surgery.33 Immunotherapy is recommended after surgery so that

the allergic load is reduced.34-37 Patients who receive immunotherapy

after surgery for AFS have a better clinical outcome than those who

have received immunotherapy before surgery.38 Multiple fungal antigen

immunotherapy, as well as immunotherapy to all other positive

allergens, is advocated.38-40

Cultures are not uniformly positive, and culture techniques may miss

certain " mold " subtypes.31 Skin testing for reactivity to several

locally pervasive molds is suggested. Systemic antifungal agents have

many known negative side effects, and because there are no good

studies to prove their effectiveness in this disease, their

usefulness is limited.41 Topical antifungals may be of benefit;

studies are underway to prove this.42,43 AFS recidivism is well

recognized, and a combination of both medical and surgical management

is the best way to treat this difficult disease.33

Churg-Strauss Syndrome

Churg-Strauss syndrome is a vasculitis characterized by asthma, 10%

peripheralblood eosinophilia, pulmonary infiltrates, and paranasal

sinus abnormalities (1990 criteria). Extravascular eosinophils may be

seen. Fifty percent of patients with Churg-Strauss syndrome have

nasal polyps.45,46 In recent years, leukotriene modifiers used for

the treatment of asthma, with the potential benefit for allergic

rhinitis, were of concern because of a possible correlation between

Churg-Strauss syndrome and the use of these agents. However, a review

in CHEST noted no such correlation.47 Conventional wisdom suggests

that underlying Churg-Strauss vasculitis is unmasked when a patient's

steroid therapy for asthma is tapered as a result of leukotriene

modifier use.

Young's Syndrome

Young's syndrome is a triad of chronic sinusitis, azoospermia, and

nasal polyposis.48

Nonallergic Rhinitis With Eosinophilia Syndrome

This entity is found in patients who have rhinorrhea but negative

skin-prick test reactions to allergens. Yet, nasal lavage indicates

the presence of eosinophils. These patients respond to nasal

corticosteroids. Nineteen percent of these patients have nasal

polyps.49 Nonallergic rhinitis with eosinophilia syndrome is not IgE-

mediated in a manner consistent with allergic rhinitis. A careful

clinician should determine that antihistamines and topical

corticosteroids have been discontinued prior to skin-prick testing to

avoid a false-negative result.49

Sarcoidosis

Although not a classic common finding on physical examination, there

are three articles in the literature describing nasal polyp resection

yielding a diagnosis of sarcoidosis from histologic examination. On

occasion, systemic sarcoidosis was later diagnosed.50-52

Clinical Symptoms

Patients with nasal polyposis may visit a physician because of a

chief complaint of an inability to breathe through the nose.53 They

may have a hyponasal voice (rhinophonia clausa).54 Hyposmia or

anosmia is common as well, as is dysgeusia. Snoring can occur as a

result of upper airway obstruction, as can postnasal drip/rhinorrhea,

cough, and/or headache.3-5

Physical examination of the anterior nares with a standard office

speculum may miss a nasal polyp, especially when it only occupies the

middle meatus. A diagnostic nasal endoscopy may be necessary. Nasal

polyps are often pearly, glistening, pale gray, smooth and

semitranslucent (Fig 4). They attach from a pedicle and arise from

the ostiomeatal complex, most often from the uncinate process of the

ethmoid bone and the middle turbinate.56

The differential diagnosis of nasal polyps in adults includes benign

tumors such as inverting papilloma or antrochoanal polyp, and

malignant tumors such as squamous cell or adenocarcinoma (Table 1).

Diamantopoulos et al57 reviewed 2,021 nasal polyps biopsied from 1991

to 1999 and noted that 22 cases (1.1%) had a different ultimate

diagnosis based on histology. In children, the presence of nasal

polyps automatically requires a sweat test to rule out cystic

fibrosis.58 The differential diagnosis of nasal polyposis in children

also includes meningocele, encephalocele, and glioma.12,59-60

Histology, Pathogenesis, and Grading

Typically, histologic analysis of tissue from nasal polyps shows

edema and eosinophilia. In a series of 95 resected nasal polyps,

sson and Hellquist5 found that 82 polyps displayed the usual

edema/eosinophilia pathology (Fig 5), 7 were

neutrophilic/fibroinflammatory, 5 had hyperplasia of seromucinous

glands, and 1 indicated atypical stroma. Tissue eosinophilia is seen

in 80 to 90% of cases.62 Regulated on activation, normal T-cell

expressed and secreted (RANTES) is a chemokine that, along with

eotaxin and interleukin-5, mediates migration of eosinophils into the

lamina propria of nasal polyps.62,63 There is hyperplasia of

sebaceous glands. Nasal washings show neutrophilia in 7% of cases,

especially in patients with CF, primary ciliary dyskinesia, or

Young's syndrome. Mast cells are present. Often, as mentioned above,

the histology points to a non-IgE-mediated mechanism.5,12(p1026)

Basic fibroblast growth factor has been localized to nasal polyps and

may contribute to the pathology of the disease.64 Similarly, matrix

metalloproteinase-1 and matrix metalloproteinase-9 have been noted to

be expressed in areas of matrix degradation in nasal polyp

fibroblasts.65,66 Glucocorticoid receptors and cyclooxygenase-2 (COX-

2) are present in nasal polyps; therefore, they suggest a role for

steroids (and perhaps COX-2 inhibitors) in modulating inflammation in

patients with this disease.67 Not surprisingly, nuclear factor kappa

beta, a socalled final common pathway of inflammation as a

transcriptional promotor of inflammation, has been determined to be

constitutively expressed in nasal polyps.67 Although some authors

postulate a role for food allergy in causing nasal polyps

(intradermal skin tests to food are positive in 85% of those with

polyps, compared with 11% in healthy control individuals) there has

been a lack of evidence indicating that food challenges can cause a

dose-dependent increase in nasal polyp number and size.68

Treatment

Treatment modalities for nasal polyps include medical management

alone or in combination with surgical intervention.70 Despite

advances in both medical and surgical treatment modalities, we do not

have a cure for nasal polyps. These therapies are only able to delay

the reformation of polyps. This is due to the fact that the etiology

and pathogenesis of nasal polyps are not completely understood.71

Although the use of functional endoscopic sinus surgery along with

glucocorticoids is a common treatment modality, a recurrence rate of

at least 40 to 60% is common.72,73 Indeed, nasal polyp recurrence

rates are higher in patients with asthma or aspirin intolerance and

negative skin tests.45 Persistent nasal obstruction after a course of

steroids may warrant surgery.74

The mainstay of medical management is topical steroids,75 which have

been shown to be effective in the primary treatment of nasal polyps

as well as in maintenance therapy to delay recurrence after

surgery.76 Systemic steroids can also be added, and are very helpful

during the perioperative period.77 For patients with small polyps

that are not causing significant nasal obstruction, topical

corticosteroids may be sufficient to shrink polypoid tissue and yield

symptomatic improvement. For patients with large polyps, a short

course of systemic corticosteroids combined with topical therapy may

provide relief of nasal symptoms.78

Medical treatment modalities that have been reported in the

literature but are not yet accepted as the standard of care include

the use of antileukotrienes,79 longterm low-dose macrolide therapy,80

topical capsaicin,81 topical furosemide,82 immune modification with

interferon alfa-2a,83 and, most recently, topical amphotericin B.84

For many years, the surgical management of nasal polyps consisted of

a simple intranasal snare polypectomy. The surgeon wore a headlight

and used a wire snare to remove polyps from the nasal cavity only.

This provided excellent relief of nasal obstruction, but the

recurrence rate was very high because it did not address the abnormal

tissue from within the sinuses themselves. Then in the late 1980s,

Kennedy introduced functional endoscopic sinus surgery to North

America.85 This revolutionized the surgical management of nasal

polyposis. This surgery entails using a rigid telescope with both

straight and varying angles that improve visualization within the

sinuses. These are used along with grasping and/or cutting

instruments to remove diseased tissue directly from the affected

sinuses to create open drainage pathways. A coronal CT film is placed

on a viewbox in the operating room to be used as a " road map. " The

recurrence rate after this surgery is much lower than with the

intranasal snare polypectomy, but it is still not a cure.85,86

Another surgical advancement is the use of powered instrumentation,

which has greatly improved dissection techniques.87,88 Powered

instruments suction and cut tissue precisely. This allows for a

faster and more complete removal of the visualized abnormal tissue,

while sparing the normal mucosa.87,88

Most recently, the use of CT image-guided surgery has greatly

improved the surgeon's ability to do a more complete dissection (Fig

6).90,91 Preoperatively, a special thin-cut sinus CT scan that allows

the surgeon to orient the patient in space is obtained. At surgery,

the patient is registered, and then the surgeon can point to an area

within the sinus cavity to determine if it is safe and/or necessary

to enter that particular air cell. The margin of error is

approximately 1 to 2 mm, and therefore the surgeon still must know

the complicated and varying anatomy of the paranasal sinuses.90

Summary

Nasal polyps are nasal epithelial outpouchings incited and promoted

by inflammation. Although some patients have IgE-mediated disease

with positive skin tests, others do not. Symptomatic patients may

have nasal stuffiness, perceived inability to breathe, postnasal

drip, cough, headache, anosmia, and dysgeusia. Physical examination

reveals pale, glistening lesions that sometimes require nasal

endoscopy to be recognized. Despite surgery and steroids, there is

still a high recurrence rate. Underlying disease processes—eg, IgE-

mediated disease, AFS, Churg-Strauss syndrome, CF, Kartagener's

syndrome, Samter's triad, or asthma—must be diagnosed and treated.

The pathogenesis of this eosinophilic yet avascular lesion is complex

and still incompletely understood. As we come to better understand

the etiology and pathogenesis of nasal polyps, new treatment

modalities are sure to be found that will enhance our ability to

treat this challenging disease entity. As chest physicians, we serve

our patients' health well by understanding the nuances of this

ancient disease.

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