Mucociliary Transport and Histologic Characteristics of the Mucosa of Deviated Nasal Septum

ORIGINAL ARTICLE Mucociliary Transport and Histologic Characteristics of the Mucosa of Deviated Nasal Septum

Yong Ju Jang, MD, PhD; Na-Hye Myong, MD, PhD; Keun Hwan Park, MD; Tae Woo Koo, MD; Han-Gyun Kim, MD

Objective: To investigate differences in mucociliary Results: The concave side showed longer saccharin clear- clearance, histologic characteristics, and surface struc- ance time than the convex side and revealed much more ture of the bilateral nasal septal mucosa in patients with severe loss of cilia. Inflammatory cells more heavily in- nasal septal deviation. filtrated the concave side, and seromucinous glands were less densely distributed. Design: Mucociliary transport was measured by saccharin clearance time in both nasal cavities of 20 pa- Conclusion: Concave-side septal mucosae have im- tients with nasal septal deviation. Their septal mucosae paired mucociliary transport, presumably due to ciliary were taken during septoplasty, and the ciliary popula- loss, increased inflammation, and decreased density of tion was studied by scanning electron microscopy. His- the glandular acini. tologic differences in the lamina propria of septal mucosae were compared under a light microscope. Arch Otolaryngol Head Neck Surg. 2002;128:421-424

HE SEVERITY of septal devia- peared with increased frequency on the tions, their location, shape, side opposite the septal deviation.7 and complexity all influ- Nasal mucociliary clearance is a fun- ence airflow dynamics in damental function required to maintain the the nasal cavity. Thus, in the health and defense of the nose.8 The cli- bilateralT nasal cavities of subjects with na- nician should suspect a disorder of mu- sal septal deviation (NSD), a difference may cociliary clearance in a patient who has rhi- occur in the amount of airflow and resis- nosinusitis. In the present study, we tance.1 In response to the difference in air- hypothesized that the nasal cavities of both flow dynamics between nasal cavities in sides in NSD have different mucociliary NSD, a compensatory hypertrophy of the clearances, and this difference may be re- nasal mucosa on the side of the nose op- sponsible for varying symptoms and in- posite the major septal deviation is often creased incidence and severity of sinus- found.2 In addition to the compensatory itis in the side opposite the septal deviation. hypertrophy, an impaired mucociliary To test this hypothesis, we investigated the clearance, higher incidence of ostiome- difference in saccharin clearance time atal complex obstruction, and increased (SCT) between nasal cavities. We also fur- incidence of sinusitis have been reported ther investigated the difference between in subjects with NSD.3-7 Interestingly, si- the concave- and convex-side mucosa with nusitis has been reported to be more se- respect to anatomical factors such as cili- vere in the concave side than in the con- ary population and the density of inflam- vex side,5 although a significant association matory cells and seromucous glands, with ethmoid sinus disease on the con- which can affect the mucociliary trans- vex side has been reported.6 Ostiomeatal port. complex obstruction and resultant sinusitis in the direction of septal angulation From the Departments of RESULTS were attributable to nasal septal defor- Otolaryngology (Drs Jang, 7 Park, Koo, and Kim) and mity. However, contralateral ostiome- While the mean SCT of the concave-side Histopathology (Dr Myong), atal complex obstruction was suggested to septal mucosae was significantly longer Dankook University College of be related to middle-turbinate and lateral- than that of the convex nasal cavity in the Medicine, Cheonan, Korea. nasal-wall abnormalities, which ap- patients with NSD (P=.02), the SCT was

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 PATIENTS AND METHODS dorsum. Each mucosal sample was divided in 2: one for scanning electron microscopic examination and the other for light microscopic examination. For scanning electron The study was performed with the approval of the Dan- microscopic study of the surface structure, mucosal speci- kook University Hospital ethics committee, and all the sub- mens were immediately immersed in 2.5% glutaraldehyde jects gave written informed consent. From July 1999 to in 0.1M cacodyl buffer (pH 7.4) at room temperature. Af- February 2000, we observed 20 patients (12 men and 8 ter several hours of fixation, they were rinsed in 0.1M caco- women), ranging in age from 21 to 40 years (mean±SD age, dyl buffer with 0.1M sucrose and postfixed in 1% osmium 32.8±15.23 years), who underwent septoplasty for symp- tetraxide in 0.1M cacodyl buffer (pH 7.4) at 4°C. The speci- tomatic NSD, which was diagnosed by endoscopy and acous- mens were dehydrated in graded ethanol series and then tic rhinometry. Thirteen patients showed deviation to the dried in a critical point drier (HCP-2; Hitachi Co, Tokyo, left side, and the remaining 7 patients showed deviation Japan). Samples were coated with gold in a sputter coater to the right. All patients had C-shaped anteroposterior de- (E 106; Hitachi Co) with 2.5-kV acceleration voltage in an viation and C-shaped cephalocaudal septal deviation on en- argon atmosphere with a current of 20 mA for 1 minute. doscopic examination. Patients who had minor spurs or se- Samples were examined under a scanning electron micro- vere S-shaped septal deviation were excluded. In acoustic scope (S-2500; Hitachi Co) at 15.0 kV in a random man- rhinometric examination, all patients revealed a differ- ner. The degree of ciliary population was graded as 1 (no ence of greater than 0.4 cm2 between nasal cavities in the cilia), 2 (ciliated mucosa occupying less than 30% of the nondecongested minimal cross-sectional area. Each mem- epithelial surface), 3 (ciliated mucosa occupying 30% to ber of the control group demonstrated a straight septum 60% of the surface), or 4 (ciliated mucosa occupying more on endoscopic examination and showed a difference in mini- than 60% of the epithelial surface). To evaluate the degree mal cross-sectional area of less than 0.2 cm2, as deter- of ciliary population, the proportional area of the ciliated mined by acoustic rhinometry. The study population had epithelial surface was estimated by 2 separate investiga- not experienced upper respiratory tract infection in the pre- tors on 5 randomly selected mucosal surfaces for each speci- vious 2 months, and showed normal sinus radiography char- men under ϫ1500 magnification. acterized by the absence of sinus opacity, mucosal thick- For light microscopic examination, the remaining mu- ening, and air-fluid level in the posteroanterior view and cosal pieces were fixed in 10% formalin, embedded in par- the Water view. They showed negative results in a skin- affin, and stained with hematoxylin-eosin. The histologic prick test using 40 common inhalant allergens, as deter- characteristics observed included the distribution of the na- mined by a mean wheal size smaller than 2 mm in diam- sal glands and infiltration of inflammatory cells. The num- eter and an area less than 25% that of a reference histamine ber of all types of inflammatory cells was noted in 5 ran- reaction. domly selected areas of both the subepithelial layer and the During the preoperative evaluation, saccharin tests of interglandular connective tissue at ϫ400 magnification. The both nasal cavities were conducted separately on consecu- distribution of nasal glandular tissues was evaluated in the tive days. A 1-mm-diameter or quarter fragment of a sac- portions of lamina propria deeper than the subepithelial charin tablet was placed on the anterior end of the septal layer by counting the number of glandular acini on the ran- mucosa, just medial to the anterior end of the inferior tur- domly selected 5 areas at ϫ400 magnification. The glan- binate. The patient was asked to sit quietly, head forward, dular acini were also classified into serous and mucinous and not to sniff, sneeze, eat, or drink. The time taken to types. The serous and mucinous glands were character- the first perception of the sweet taste was recorded. As a ized by their amphophilic granular cytoplasms and pale blue control, the saccharin test was also performed in 15 healthy or clear cytoplasms, respectively. Light microscopic ex- volunteers (aged 19-38 years). The control population also amination was also conducted in a blind manner by 2 in- had a normal sinus radiograph, negative results in the skin- vestigators. The difference in SCT was statistically tested prick test, and no history of recent upper respiratory tract by 1-way analysis of variance using the PC-SAS statistical infection. package, version 6.04 (SAS Institute, Cary, NC). The dif- During the septoplasty, samples of septal mucosae ference in the degree of ciliary population, number of in- approximately 0.5ϫ0.5 cm were taken from the point 2 flammatory cells, and number of glandular acini was sta- cm posterior to the nostril and 1.5 cm inferior to the nasal tistically tested using the t test.

those of the septal mucosa of the right and left side of Table 1. Mean ± SD Saccharin Clearance Time (SCT) the normal group, respectively (PϾ.05) (Table 1). in Bilateral Nasal Mucosa of Patients With Nasal Septal Deviation (NSD) and Control Subjects In scanning electron micrographic examination, the concave-side nasal mucosa (Figure 1A) showed less Patient Group Nasal Cavity Mean SCT, min dense ciliary population than the contralateral septal mucosa (Figure 1B). The average score in the grading of cili- NSD (n = 20) Concave side 16.52 ± 8.06 ary population was significantly lower in the concave sides, Convex side 12.36 ± 4.83 Control (n = 15) Right side 11.36 ± 4.33 indicating more severe loss of cilia (P=.005) (Table 2). Left side 11.06 ± 3.53 The mean±SD number of infiltrating inflammatory cells was 52.9±4.95 in the convex side of the septal mucosa and 102.5±51.8 in the concave-side septal mu- not significantly different between both nasal cavities in cosa (P=.003) (Figure 2). Infiltrating inflammatory cells the control group. The SCT in the convex side of pa- were largely lymphocytes, histiocytes, plasma cells, and tients with NSD showed no significant difference with neutrophils.

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Figure 1. In scanning electron micrographs of the septal mucosa from each nasal opening in a patient with nasal septal deviation, the convex side (A) shows sparsely populated cilia (original magnification ϫ1990), and the concave side (B), densely populated cilia (original magnification ϫ2180).

140 Table 2. Grade Scores of the Ciliary Population Under Scanning Electron Microscope of Each Nasal Cavity 120 * of Patients With Nasal Septal Deviation 100 Concave Side Convex Side Grade* (n = 20) (n = 20) 80

17260 2105 33840 405No. of Inflammatory Cells Mean ± SD 1.8 ± 0.69 2.8 ± 0.95† 20

*Grade 1 indicates no cilia present; grade 2, cilia occupy less than 30% of 0 the epithelial surface; grade 3, cilia occupy 30% to 60% of the epithelial Concave Convex surface; and grade 4, cilia occupy more than 60% of the epithelial surface. Nasal Cavity †P = .005 by the t test. Figure 2. Comparison of the mean ± SD number of inflammatory cells infiltrating the concave and convex nasal cavities in patients with nasal septal deviation. Inflammatory cells more heavily infiltrated the concave side The mean±SD number of submucosal glandular acini (asterisk indicates P=.003 by the t test). was 97.2 ± 16.9 on the convex-side septal mucosa and 66.6 ± 18.7 on the concave-side septal mucosa, indicating ciliary transport (MCT) was normalized 3 months after sparse distribution of glandular acini in the concave-side septoplasty.3 In contrast, Passali et al8 found that times septal mucosa (Figure 3). Among the total glandular acini, for MCT in patients with NSD were practically identical the respective numbers of mucinous glands and serous to those of the control group. This discrepancy in the re- glands also were smaller in the concave-side mucosa sults of the previous studies may exist because the MCTs (PϽ.001). of the bilateral nasal cavities were not considered inde- pendently. However, in our study, we compared the MCT COMMENT of the each nasal cavity and found impaired SCT in only the concave nasal cavity. In the present study, the SCT was longer in the concave In our study, the concave-side septal mucosae re- nasal cavity than in the convex nasal cavity. Previous in- vealed more severe loss of cilia under scanning electron vestigators have also reported significantly increased SCT microscopic examination. Ultrastructural changes of res- in patients with NSD.3,4 Furthermore, prolonged muco- piratory mucosa can result from acute and chronic in-

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 12,13 120 * cilia, and mucus quality. The results of our study, Concave which revealed impaired MCT in the concave nasal cav- Convex 100 * ity, can certainly be explained by the decreased ciliary population on the ipsilateral side, indicating a loss of mu- 80 cociliary machinery. Additionally, a changed property of mucus covering the epithelium that can result from in- 60 creased inflammatory infiltrates and reduced distribution of glandular tissue (not examined in our study) might 40 No. of Nasal Glands have contributed to the impaired MCT in the concave- * side septal mucosa. 20 In conclusion, the results of our study suggest that NSD is not a simple affliction resulting only in a me- 0 SerousMucinous Total chanical alteration of nasal airflow in the nasal cavity, but Gland Type a more complex disease process presenting with impaired mucociliary clearance in the concave-side mu- Figure 3. Comparison of the mean ± SD numbers of nasal glands in the concave and convex nasal cavities in patients with nasal septal deviation. cosa that can predispose a patient to increased inci- There were significantly more nasal glands in the convex cavity (asterisks dence and severity of sinusitis in the side opposite the indicate PϽ.001 by the t test). NSD. The results of this study also indicate that the concave-side septal mucosa has impaired MCT compared with fections.9 In experimental study in which one nostril is that of the convex side, probably due to ciliary loss, in- closed and the other is open, ciliary loss in the open cav- creased inflammation, and decreased density of the glan- ity has been demonstrated.10 Accordingly, in our study, dular acini. the increased loss of epithelial cilia in the concave-side septal mucosa might have been caused by increased air- Accepted for publication October 2, 2001. flow. Corresponding author and reprints: Han-Gyun Kim, In the present study, infiltration of inflammatory cells MD, Department of Otolaryngology, Dankook University was more prominent in the concave-side sepal mucosa College of Medicine, Anseo-Dong 29, Cheonan-City, Choong- than in the convex. The exact mechanism for this occur- nam-Do, Korea 330-714 (e-mail: [email protected]). rence is not understood, but it may be that a spontane- ous inflammatory process not related to allergy or infec- REFERENCES tion may be brought about in the more open nasal cavity by increased airflow. 1. Cole P, Chaban R, Naito K, Oprysk D. The obstructive nasal septum: effect of In the study by Inagi11 regarding the histologic simulated deviations on nasal airflow resistance. Arch Otolaryngol Head Neck changes in the mucous membrane of the human devi- Surg. 1988;114:410-412. 2. Illum P. Septoplasty and compensatory inferior turbinate hypertrophy: long- ated nasal septum, the mucosa of the concave side col- term results after randomized turbinoplasty. Eur Arch Otorhinolaryngol. 1997; lected from 74 cadavers consistently showed hypertro- 1:89-92. phic change of the area of mucous glands and the 3. Ginzel A, Illum P. Nasal mucociliary clearance in patients with septal deviation. thickness of the mucoperiosteum. However, in our Rhinology. 1980;18:177-181. study, the distribution of seromucinous glands was less 4. Ishikawa Y, Kawano M, Honjo I, Amitani R. The cause of nasal sinusitis in patients with cleft palate. Arch Otolaryngol Head Neck Surg. 1989;115:442- compact in the concave-side septal mucosa than on the 446. convex side. The different result regarding the distribu- 5. Suzuki H, Yamaguchi T, Furukawa M. Rhinologic computed tomographic evalu- tion of nasal glandular tissue between the 2 studies may ation in patients with cleft lip and palate. Arch Otolaryngol Head Neck Surg. 1999; result from the different study populations. In our 125:1000-1004. 6. Calhoun KH, Waggenspack GA, Simpson CB, Hokanson JA, Bailey BJ. CT evalu- study, the study materials were septal mucosa taken ation of the paranasal sinuses in symptomatic and asymptomatic populations. from symptomatic living human subjects with NSD. Otolaryngol Head Neck Surg. 1991;104:480-483. Thus, our result may better represent the true histologic 7. Elahi MM, Frenkiel S, Fageeh N. Paraseptal structural changes and chronic si- features of subjects with NSD complaining of stuffy nus disease in relation to the deviated septum. J Otolaryngol. 1997;26:236-240. nose that necessitates surgical treatment. As for the 8. Passali D, Ferri R, Becchini G, Passali GC, Bellussi L. Alterations of nasal mucociliary transport in patients with hypertrophy of the inferior turbinates, devia- decreased distribution of the glandular tissue in our tions of the nasal septum and chronic sinusitis. Eur Arch Otorhinolaryngol. 1999; study, it is possible that a chronic inflammatory process 256:335-337. of the concave-side septal mucosa, as demonstrated in 9. Rautiainen M, Nuutinen J, Kiukaanniemi H, Collan Y. Ultrastructural changes in our study as an increased infiltration of inflammatory human nasal cilia caused by the common cold and recovery of ciliated epithelium. Ann Otol Rhinol Laryngol. 1992;101:982-987. cells, may lead to stromal proliferation and fibrosis of 10. Tos M, Mogensen C. Changes of the nasal mucosa in altered airflow illustrated the lamina propria, resulting in relative paucity of the by blind quantitative histology. J Laryngol Otol. 1978;92:667-680. glandular acini. 11. Inagi K. Histological study of mucous membranes in the human nasal septum. The MCT represents the first barrier of the nasal fos- Nippon Jibiinkoka Gakkai Kaiho. 1992;95:1174-1189. sae and paranasal sinuses against various biological and 12. Toskala E, Nuutinen J, Rautiainen M, Torkkeli T. The correlation of mucociliary transport and scanning electron microscopy of nasal mucosa. Acta Otolaryngol physical insults. Differences in MCT rates between dif- (Stockh). 1995;115:61-65. ferent sites in the nose depend on ciliary beat fre- 13. Lale AM, Mason JDT, Jones NS. Mucociliary transport and its assessment: a re- quency, density of the ciliary population, length of the view. Clin Otolaryngol. 1998;23:388-396.

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Accepted for publication January 9, 2002. fifteen years’ experience at the Children’s Hospital of Philadelphia. In: Sanna M, This study was presented at the 15th Annual Meeting ed. Cholesteatoma and Mastoid Surgery. Rome, Italy: CIC Edizioni Internazion- ali; 1997:422-431. of the American Society of Pediatric Otolaryngology, 5. McGill TJ, Merchant S, Healy GB, Friedman EM. Congenital cholesteatoma of the Orlando, Fla, May 10, 2000. middle ear in children: a clinical and histopathological report. Larynogoscope. We greatly appreciate the efforts of Scott J. Beam in 1991;101:606-613. the preparation of the manuscript. 6. Levenson MJ, Michaels L, Parisier SC, Juarbe C. Congenital cholesteatomas in children: an embryologic correlation. Laryngoscope. 1988;98:949-955. Corresponding author: Peter J. Koltai, MD, Section of 7. Rizer FM, Luxford WM. The management of congenital cholesteatoma: surgical Pediatric Otolaryngology, The Cleveland Clinic Foun- results of 42 cases. Laryngoscope. 1988;98:254-256. dation, 9500 Euclid Ave, Desk A71, Cleveland, OH 44195 8. House JW, Sheehy JL. Cholesteatoma with intact tympanic membrane: a report (e-mail: [email protected]). of 41 cases. Laryngoscope. 1980;90:70-76. 9. McDonald TS, Cody DTR, Ryan RE. Congenital cholesteatoma of the ear. Ann Otol Rhinol Laryngol. 1984;93:637-640. REFERENCES 10. Zappia JJ, Wiet RJ. Congenital cholesteatoma. Arch Otolaryngol Head Neck Surg. 1995;121:19-22. 1. Derlacki EL, Clemis JD. Congenital cholesteatoma of the middle ear and mas- 11. Koltai PJ, Nelson M, Castellon RJ, et al. The natural history of congenital cho- toid. Ann Otol Rhinol Laryngol. 1965;74:706-727. lesteatoma. Arch Otolaryngol Head Neck Surg. 2002;128:804-809. 2. Friedberg J. Congenital cholesteatoma. Laryngoscope. 1994;104(pt 2):1-24. 12. Parisier SC, Weiss MH. Recidivism in congenital cholesteatoma surgery. Ear Nose 3. Grundfest KM, Ahuja GS, Parisier SC, Culver SM. Delayed diagnosis and fate of Throat J. 1990;70:362-364. congenital cholesteatoma (keratoma). Arch Otolaryngol Head Neck Surg. 1995; 13. Ino Y, Imamura Y, Hiraishi M, Yabe T, Suzuki JI. Mastoid pneumatization in chil- 121:903-907. dren with congenital cholesteatoma: an aspect of the formation of open-type and 4. Potsic WP, Wetmore RF, Marsh RR. Congenital cholesteatoma of the middle ear: closed-type cholesteatoma. Laryngoscope. 1998;108:1071-1076.

Correction

In the article by Jang et al titled “Mucociliary Transport and Histologic Char- acteristics of the Mucosa of Deviated Nasal Septum” in the April 2002 issue of the ARCHIVES (2002;128:421-424), the legend for Figure 1 was incorrect. It should have read as follows:

Figure 1. In scanning electron micrographs of the septal mucosa from each nasal opening in a patient with nasal septal deviation, the concave side (A) shows sparsely populated cilia (original magnification ϫ1990), and the convex side (B), densely populated cilia (original magnification ϫ2180).

We regret the error.

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