Nasal polyposis in a chimpanzee

Robert L. Jacobs, M.D., Gregory K. Lux, M.D., Richard L. Spielvogel, M.D.,

Jorg W. Eichberg, D.V.M., Ph.D., and Chester A. Gleiser, V.M.D. San Antonio, Texas

A 15.year-old female chimpanzee with nasal polyposis sustained respiratory compromise when she was sedated and expired despite resuscitative efforts. Postmortem examination revealed very large J1:bromyxomatous nasal polyps completely obstructing the upper airway. Gross examination und histopathologic jindings were indistinguishable from those of human polyps. The chimpanzee is a potential animal model for nasal polyposis that could provide basic information concerning the relationship of polyps to type I hypersensitivity and to rhree severe respiratory tract disorders in humans: cystic fibrosis, bronchial asthma, and the immotile cilia syndrome. (J ALLERGY CLIN IMMUNOL 74:6/, 1984.)

Nasal polyposk is seemingly an uncommon occur- rence in animals. Scattered reports document that cat- tle, sheep,’ horses,* cats,3 and chimpanzees4 are rarely affected with polypoid lesions that grossly re- semble nasal polyps from humans. Scant histologic descriptions make it difficult to ascertain whether these polyps are identical between genera of animals.

We confirm that chimpanzees spontaneously de- velop nasal polyps and extend this observation to demonstrate that they are histologically identical to human nasal polyps. Such an animal model for nasal polyposis could provide basic information concerning the relationship of this structure to type I hypersensi- tivity and to three severe respiratory tract disorders in humans: cystic fibrosis, bronchial asthma, and immo- tile cilia syndrome.

Case report

A 1%year-old adult female chimpanzee, (Olive), was noted to have nasal polyposis at age 10 yr during evaluation of a purulent nasal discharge. She tolerated the untreated

From the Department of Allergy-Immunology and the Department of Dermatology, Division of Medicine, Wilford Hall United States Air Force Medical Center, and the Department of Mi- crobiology and Infectious Disease and Department of Laboratory Animal Resources, Southwest Foundation for Research and Edu- cation, San Antonio, Texas.

Received for publication Aug. 25, 1983. Accepted for publication Jan. 11, 1984. Reprint requests: Robert L. Jacobs, M.D., Chairman, Department

of Allergy-Immunology, Division of Medicine, Wilford Hall USAF Medical Cetner, Lackland Air Force Base, Texas 78236.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of the Air Force or The Department of Defense.

FIG. 1. The largest polyp was 10 cm in length and 3 cm in its largest diameter. The surface was pale and glistening. The cut surface revealed a grey semitranslucent, edema- tous, jelly-like material.

polyps well over the next 5 yr with increasing nasal obstruction as the only observed manifestation. There were no apparent lower respiratory tract symptoms or signs. Two pregnancies resulted in full-term healthy offspring during this period. In the second pregnancy the polyps totally obstructed the upper respiratory tract requiring continuous mouth breathing. After delivery of the second infant, Olive was sedated in order to transport her to a different locale. While she was sedated, she suffered respiratory tract com- promise resulting in cardiac and respiratory arrest. Despite resuscitative efforts, she expired. On gross inspection dur- ing the postmortem examination, the nasal polyps were in- distinguishable from similar lesions of humans (Fig. 1).

Histopathology

The histopathologic findings were as noted (Figs. 2 and 3). No significant histologic difference was noted when this

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62 Jacobs et al. J. ALLERGY CLIN. IMMUNOL. JULY 1984

FIG. 2. There was a normal pseudostratified columnar epithelium that rested on a basement membrane that was not thickened. Areas of invagination were found, but no true inclusion glands were noted. The connective tissue stroma was markedly edematous with collagen ac- cumulation in the perivascular areas. There was an even dispersion of inflammatory cells among the reticular network of ground substance.

FIG. 3. Areas were found of partial or complete denudation in which the basement membrane appeared intact. No areas of squamous metaplasia or frank ulceration were found. The scattered inflammatory cell infiltrate was composed of approximately equal numbers of neutrophils, eosinophils, and mononuclear cells. Occasional multinucleated giant cells and plasma cells were noted. No atypical fibroblasts were seen.

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chimpanzee polyp was compared with human nasal polyps. Histologic examination of other organs including the lungs, kidneys, skin, and the intestinal tract failed to reveal any pathologic process.

Laboratory data

Total serum IgE, RAST to 21 south Texas aeroallergens, total serum IgG, IgA, and IgM, complement components C3, C4, and CH50 were obtained on Olive’s stored serum by use of standard techniques and antisera directed toward human protein.;’ AYI these assays were negative or within normal limits except for a markedly elevated total serum IgE of 1526 IU/ml

Duplicate RAS’T batteries were obtained on five adult male and five adult female chimpanzees of similar age and aeroallergen exposure. One chimpanzee demonstrated a class 3 RAST to gralss and a class 2 RAST to ragweed. The nine remaining sera demonstrated no RAST activity.

DISCUSSION

Nasal polyps are benign fibromyxomatous growths occurring in the nose and paranasal sinuses of humans causing the highest morbidity and mortality of any form of chronic rhinitis. Morbidity is very high sec- ondary to the complications of the obstructed upper airway. Recurrent and chronic sinusitis are commonly seen as polyp growth obstructs sinus duct ostia.6 Mor- tality is usually reported to be associated with surgical efforts toward polyp control.‘. 8

Although nasal polyps have been reported since Hippocrates’ time.,‘j little is known of the pathogene- sis. Several postulates have been studied without any theory having gained wide acceptance. Chronic in- flammation, believed by many to be central to the pathogenesis,” can be demonstrated very commonly upon histologic examination of polyps. Clinical evi- dence suggests that stasis of secretions and mucous membrane edema lead to paranasal and intranasal mucosal surface infections.g The relationship of the eosinophilic-associated inflammation to polyp forma- tion remains unclear. Type I hypersensitivity immu- nologic findings occur in approximately 50% of hu- mans with nasal polyp~‘~-‘~; yet there is frequently a lack of clinical correlation.*O, “2 I3

Nasal polyps are often associated with an underly- ing chronic respiratory tract disorder. Certain patients with bronchial asthma in whom aspirin ingestion trig- gers significant bronchospasm commonly have polyps of the upper airway. ‘I. ‘* Patients with cystic fibrosis,‘j particularly adults, have an increased inci- dence of nasal pol:yps. Finally, patients with the im- motile cilia syndrome have been reported to have as- sociated nasal polyps. I6

The finding in this animal of an increased total IgE has uncertain meaning. Symptoms suggestive of al- lergic respiratory tract disease were not observed by

Nasal polyposis in chimpanzee 63

either l:he caretakers or the veterinary physicians in attendance, and a RAST to common aeroallergens was repeatedly negative. Elevated total IgE could have been the result of systemic parasitosis; however, there was no additional clinical or laboratory evidence of infestation during life or post mortem.

Naturally occurring animal models of human dis- ease immeasurably aid research efforts concerning basic mechanisms of pathogenesis. The discovery of nasal polyps in a chimpanzee, grossly and histologi- cally identical to human polyps, may be a critical factor to provide basic information concerning the re- lationship of this structure to type I hypersensitivity and to three severe respiratory tract disorders in hu- mans: cystic fibrosis, bronchial asthma, and immotile cilia syndrome.

We acknowledge with appreciation the technical assis- tance of Ms. Gladys A. Stephens and the administrative efforts of Ms. Sharon L. Kline in the preparation of this manuscript.

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