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1 Deleterious effect of smoking and nasal septal deviation on mucociliary clearance and improvement after septoplasty Murat Karaman, M.D.,* and Arman Tek, M.D.# ABSTRACT Objectives: To investigate the effect of septal deviation, septoplasty, and smoking upon nasal mucociliary clearance by using saccharine test. Methods: Included in this study were 40 patients (15 women and 25 men) who had septal deviation and septoplasty surgery performed between March and June Patients are classified into three groups: group I (n 20) nonsmoking patients who had septoplasty surgery, group II (n 20) smoking patients who had septoplasty surgery, and the control (n 20) group. None of the control group has nasal breathing problem or smoking history. For determining preoperative and postoperative nasal mucociliary clearance (MCC) time, a saccharine test was performed on the patients 1 day before surgery and at the third month of postoperative control. Results: Preoperative and postoperative nasal MCC time in patients of group I are statistically significantly lower than the group II (p 0.01). Postoperative MCC time in group I and II is significantly decreased compared with preoperative MCC time, statistically (p 0.01). Preoperative and postoperative MCC time of group I and group II is significantly higher than MCC time of the control group (p 0.01). Conclusion: Nasal septal deviation and smoking deteriorates nasal MCC time and this result can be shown easily with the saccharine test. Properly performed septoplasty surgery decreases nasal MCC time during the late postoperative period but MCC times are still longer than normal. The saccharine test can be used for following up the effect of septoplasty upon nasal mucosa. (Am J Rhinol Allergy 23, 2 7, 2009; doi: /ajra ) Key words: Nasal mucociliary clearance, postoperative, preoperative, saccharine test, septal deviation, septoplasty, smoking Cleaning foreign particles over respiratory mucosa and keeping this mucosa moist are necessary for normal physiology of the nose. These abilities of respiratory mucosa depend on effective ciliary activity and renewing of airway secretions. These are together known as mucociliary activity. It is known that long-term smoking causes an alteration in mucociliary clearance (MCC) by decreasing normal cilia population and impairing viscoelasticity of mucus. 1 Nasal septal deviation alters nasal physiology by causing obstruction. In addition, deviation disturbs MCC by increasing mucus secretion, effecting normal ciliary movement, and causing airway epithelium damage. 2,3 The first defense mechanism for the airway is at the nasal fossa mucosa. This mechanism depends on the synergia of mucus and cilia, which create MCC. Technological improvements have made it possible for us to determine the nasal dynamic phenomena such as nasal transport function abnormalities within the past 20 years. Surgery is the only curative treatment for nasal septal deviation. In some literatures it is emphasized that septoplasty effects MCC positively. 4,5 Alteration on nasal mucosa can be investigated with the following mucociliary function studies: The photometrical method can be used for measuring ciliary movements by evaluation of cilia beat frequency from randomly selected areas in nasal mucosa. In this method, ciliary movements can be measured away from hormones, inflammatory mediators, and stress. 6 8 From the *Department of Otorhinolaryngology, Umraniye State Hospital for Research and Training, Umraniye/İnstanbul and #Department of Otorhinolaryngology, Haydarpasa State Hospital for Research and Training, Üsküdar/İstanbul, Turkey Address correspondence and reprint requests to Murat Karaman, M.D., Umraniya State Hospital for Research and Training, Umraniya/İstanbul, Turkey address: karaman1398@yahoo.com Copyright 2009, OceanSide Publications, Inc., U.S.A. The MCC test is used to measure the elimination of inhaled aerosols Saccharine test is one of the methods used for measuring MCC. 12,13 The electron microscope can be used to evaluate histological properties of cilia. The number of united cilia, central and peripheral microtubulus defect, inner and outer dynein, and ciliary orientation can be investigated in this method. 2 The purpose of this study is to investigate the effect of septal deviation, septoplasty, and smoking on nasal MCC by using the saccharine test. MATERIALS AND METHODS In total, 40 patients (15 women and 25 men) are included in this study who underwent septal deviation and septoplasty surgery between March and June 2006 at the Haydarpasa Numune Research and Training Hospital. Twenty patients had a history of smoking (minimal, 1 pack/day; a history of at least 5 years smoking) and 20 patients did not use cigarettes. Twenty volunteers were chosen as control group and none of them had nasal pathologies or smoking history. We did not encounter any pathologies like septal deviation, rhinosinusitis, nasal polyposis, etc. during the nasal rhinoscopic examination of the control group. Diagnosis of septal deviation was based on history of patients and complete nasal examination including anterior rhinoscopy and nasal endoscopy (0 rigid endoscope). Patients with conchal hypertrophy, allergic rhinitis, bacterial or viral rhinitis, allergic pulmonary disease, asthma, sinusitis, nasal polyposis, or using drugs (topical or systemic) were excluded from the study. No medical therapy is given at preoperative period. For determining preoperative nasal MCC time, sac- 2 January February 2009, Vol. 23, No. 1

2 Table 1 Evaluation of mucociliary clearance (MCC) preoperatively and postoperatively MCC Group I (n 20)* Group II (n 20)* p# Preoperative Postoperative Preop-Postop p #Student s t-test. Paired sample t-test. p charine testing is performed on the patients 1 day before surgery. One milligram per kilogram of pethidine HCL and 0.5 mg of atropine sulfate are given intramuscularly for premedication and Cottle septoplasty surgery is done under local anesthesia on all patients. Twenty milligrams of lidocaine HC1 (2%) and mg adrenalin within 1 ml known as Jetocaine (Adeka, Istanbul, Turkey) solution is diluted at a ratio of 1:2 saline physiological solution and used for local anesthesia. Classic Killian incision was performed and bilateral mucoperichondrium was elevated. After elevation, minimal cartilage excision was made and maxillary crest was excised in all patients. During the 3-month follow-up period none of the patients had septal perforation. The patients did not have any additional nasal surgery (inferior turbinate or sinus) during septoplasty. At the end of the surgery Merocel packs (Medtronic, Mystic, CT) were used in 18 patients and nasal packs were used in 22 patients. Nasal and Merocel packs were removed at the end of 2nd day after surgery. In addition, oral antibiotics were applied for 2 days postoperatively. After nasal packs and Merocel packs were removed saline solution was ordered three times a day for 2 weeks for irrigation of the nose and patients were discharged. All patients were called back for postoperative controls at the 1st week and 1st and 3rd months. All postoperative patients were evaluated with anterior rhinoscopy (0 endoscopy), secretions were aspirated and mucosal synechiae were dissected under local anesthesia during each control. Saccharine test was performed on all patients for determining nasal MCC time at the 3rd month of control and was done while patients were not using saline solutions because they may deteriorate the test results. Saccharine testing was performed preoperatively and postoperatively on 40 patients who underwent septoplasty surgery. In addition, it was performed on 20 patients in the control group for determining MCC time. Next, average MCC time was calculated in 40 patients preoperatively and postoperatively in groups 1 and 2, and these average values were compared to evaluate the effects of smoking and septoplasty on nasal MCC (Table 1). Saccharine testing was performed on all patients and the control group for determining nasal MCC time. Patients were evaluated according to their average MCC values to determine if there was any significant difference between the smoking and the nonsmoking group. MCC Testing MCC testing was done under normal room temperature and patients were told to sit comfortably with their heads in a slightly extended position. At first, nasal secretions were aspirated and then a mm dimensional ( 1 4 saccharine tablet) saccharine tablet was positioned to the anterior border of the medial surface of the inferior turbinate in the deviated or opposite nasal cavity. Patients were told not to sneeze and not to bend forward during saccharine test. Also all patients were requested to gulp for every 30 seconds and tell whenever they felt the taste. The values were rolled up to the closest half minute and accepted as nasal MCC time. Statistical Findings The Statistical Package for Social Sciences (SPSS, Inc., Chicago, IL) for Windows 15.0 program was used for statistical analysis and paired sample t-test was used for comparison of the patients in the same group. Data values are expressed as mean SD and Student s t-test was used for comparison of the quantitative data between the two groups. One-way ANOVA test was used for comparison of the quantitative data between three groups. For the qualitative data comparison chi-square test was used. Differences were considered as significant when p RESULTS Patients were classified into three groups: group I (n 20), nonsmoking patients who had septoplasty surgery; group II (n 20), smoking patients who had septoplasty surgery; and control (n 20) group. The average age of the patients was years (range, years). Twenty-two (36.7%) of the patients were women and 38 (63.3%) of the patients are men. The average age of the 7 female and 13 male patients in group I was years (range, from years). The average age of the 8 female and 12 male patients in group II was years (range, years). The average age of the 7 female and 13 male patients in the control group was years (range, years; Table 2). None of the volunteers in the control group were smokers and none had nasal respiratory complaints. Statistically, there was no significant difference according to average ages (p 0.05) and distribution of gender (p 0.05) between groups. Preoperative nasal MCC time in patients of group I was statistically significantly lower than the preoperative nasal MCC time in group II patients (p.01). Postoperative nasal MCC time in patients of group I was statistically significantly lower than the postoperative nasal MCC time in group II patients (p 0.01). There was a statistically significant decrease at the postop- American Journal of Rhinology & Allergy 3

3 Table 2 Evaluation of the groups according to demographic features Group I (n 20)* Group II (n 20)* Control (n 20)* p Age# n (%) n (%) n (%) Sex Female 8 (40.0) 7 (35.0) 7 (35.0) Male 12 (60.0) 13 (65.0) 13 (65.0) #One-way ANOVA test. 2 test. Table 3 Evaluation of preoperative and postoperative mucociliary clearance (MCC) time in group I and the control group MCC Group I (n 20)* Control (n 20)* n# Preoperative Postoperative #Student s t-test. p p erative MCC time in group I when compared with preoperative MCC time (p 0.01). Also, there was a statistically significant decrease at the postoperative MCC time in group II when compared with preoperative MCC time (p 0.01). We compared patients in group I with the control group to evaluate the effect of septoplasty in nonsmoking patients on nasal MCC (Table 3). Preoperative MCC time of group I was significantly higher than MCC time of the control group (p 0.01). Postoperative MCC time of group I was significantly higher than MCC time of the control group (p and p 0.01). Postoperative MCC time of group I was significantly higher than MCC time of the control group (p and p 0.05). We compared nasal MCC time of group II with nasal MCC time of the control group to determine the effects of both smoking and nasal septum deviation on nasal MCC and to observe the improvement of nasal MCC time with septoplasty surgery (Table 4). Preoperative MCC time of group II was significantly higher than MCC time of the control group (p 0.01). Postoperative MCC time of group II was significantly higher than MCC time of the control group (p 0.01). We compared preoperative MCC time with postoperative MCC time of groups I and II and the control group to determine the relationship between these values and age (Table 5). In group I there was a 46% positive correlation between age and preoperative MCC time and this relationship was statistically significant (r 0.460; p 0.041; p 0.05). Also, there was a 51.3% positive correlation between age and postoperative MCC time and this relationship was statistically significant (r 0.513; p 0.021; p 0.05). In group II there was an 84.1% positive correlation between age and preoperative MCC time and this relationship was statistically significant (r 0.841; p 0.001; p 0.01). Also, there was a 75.9% positive correlation between age and postoperative MCC time and this relationship was statistically significant (r 0.759; p 0.001; p 0.01). In the control group there was a 64.6% positive correlation between age and MCC time and this relationship was statistically significant (r 0.646; p 0.002; p 0.01). DISCUSSION MCC is the most important defense mechanism of nasal epithelium. Harmful foreign material is held by this mucus layer and removed from the nasal cavity by ciliary movements. 14 MCC can be effected from environmental heat, 15 moisture, 16,17 partial O 2 pressure, 18 ph, 19 trauma, sulfur dioxide, 16,20 formaldehyde, ozone, chlorine, 21 smoking, 22,23 viral infections, 20 chronic sinusitis, 24,25 chronic and allergic rhinitis, 26,27 adenoid hypertrophia, 28 cystic fibrosis, 29 chronic bronchitis, 30 septum deviation, surgery, bronchial asthma, 31 and diabetes mellitus. 20 Smoking is one of the factors that adversely effects MCC by changing viscoelasticity of the mucus layer and showing ciliatoxic effects. 32,33 Vastag et al. 34 studied 71 smoking patients and found that MCC with chronic bronchitis is worse. 34 Ciliary beat frequency and physical properties of the mucus layer are two important factors that influence the effectivity of MCC. In mammalians it is known that mucus secretion of epithelial cells is under hormonal and neural control. Neural stimulus starts secretion of mucous and this stimulates ciliary beat mechanically. It has been proven that increases in mucus secretion stimulate ciliary beat but there is no proof about direct control of neural and hormonal 4 January February 2009, Vol. 23, No. 1

4 Table 4 Evaluation of preoperative and postoperative mucociliary clearance (MCC) time in group II and the control group MCC Group II (n 20)* Control (n 20)* n# Preoperative Postoperative #Student s t-test. p Table 5 Relationship between age and nasal mucociliary clearance (MCC) times Age (yr) Group I Preoperative MCC 0.460* Postoperative MCC 0.513* Group II Preoperative MCC 0.841# Postoperative MCC 0.759# Control MCC 0.646# Pearson korelasyon test; *p 0.05; #p stimulus over ciliary beat. In previous studies it has been shown that heavy smoking, bronchiectasia, asthma, atrophic rhinitis, sinusitis, and nasal polyposis obviously elongates nasal MCC time. 10,11,25,35 37 In the study of Stanley et al., 29 smoker and 27 nonsmoker patients nasal MCC times were measured by saccharine test and compared. They found that mean nasal MCC time of patients who smoke was 20.8 minutes and mean nasal MCC time of nonsmoking patients was 11.1 minutes and determined that smoking elongates nasal MCC time. They stated that smoking regularly decreases cilia number and changes viscoelastic property of mucus. 1 We also investigated the effects of smoking on MCC in our study. We found that preoperative and postoperative nasal MCC times in patients of group I (nonsmoking group) were statistically significantly lower than in the group II patients (smoking group). This finding obviously shows the negative effect of smoking on nasal MCC time in group II. Preoperative MCC time of group II was significantly higher than MCC time of the control group. This finding shows that nasal septum deviation with smoking disturbs nasal MCC. After septoplasty surgery in properly selected patients the nasal MCC time decreased at the late postoperative period but still had longer levels than in the control group (at the 3rd month). This also shows the negative effect of smoking on MCC. James et al. 38 investigated the relationship of age and nasal MCC in a study group aged years. They found that as the patient s age increases the ciliary beat frequency decreases and central microtubulus defects become more obvious. Consequently, they stated that over the age of 40 years nasal MCC time increases. Puchell et al. indicated that mucociliary activity speed in volunteers aged 54 years is lower than younger volunteers because of mucosal atrophy. 39 In the study of Mortensen et al. 40 it was found that there is no statistically significant difference between age and nasal MCC with radioactive studies. In our study in group I there was a positive correlation between age and preoperative MCC time and the relationship was statistically significant. In group II there was a positive correlation between age and preoperative MCC levels and the relationship was statistically significant. Also, in the control group there was a positive correlation between age and nasal MCC levels and the relationship was statistically significant. With these findings, we can say that when age increases also nasal MCC time prolongs. In a recent study comparing MCC time of different ethnic groups with Chinese people, it was found that nasal MCC time of healthy Chinese people was significantly lower than other ethnic groups. 41 In our study, all of the patients belong to the same ethnic origin. Today, two groups of methods are used for measuring nasal MCC time. First, one contains a direct method such as a stroboscopic, microcinematographic, or microossilographic method to observe ciliary movements. The second group is based on an indirect method, observing the movement of the mucosal layer from anterior to posterior with various indicators and measuring MCC time. Indirect methods include the saccharine test and Tc 99 m studies. In our study, we preferred the saccharine test because it can be obtained more easily and it is more economical than Tc99 m. David et al. used saccharine sky blue to evaluate the MCC time. They judged that if the septoplasty surgery is successfully performed, nasal MCC significantly improves. They also found that there is no significant difference in MCC time between obstructed nasal cavity and the opposite side of the patients with deviated septum. 42 In our study we selected the test side randomly. Ginzel and Illum 43 evaluated 22 patients with deviated nasal septum as the study group and 60 volunteers as a control group. In this study, it was found that with properly performed septoplasty surgery nasal MCC time significantly decreased. In addition, some animal studies showed that after sinus surgery MCC time also decreases significantly. 10 Shone et al. 44 showed that MCC in nasal cavity improved after septoplasty and endoscopic sinus surgery for nasal polyposis. We found that preoperative and postoperative nasal MCC time in group I (nonsmoking group with septal deviation) was statistically significantly higher than the nasal MCC time of the control group. These findings reveal that nasal obstruction caused by septal deviation alone disturbs nasal MCC, resulting with longer MCC time. MCC time was decreased at the late postoperative period, but did not reach the level of the control group at the 3rd month. These findings correlate with literature studies. 1,41,43 American Journal of Rhinology & Allergy 5

5 In some studies it was determined that nasal MCC was found disturbed at early postoperative periods of septoplasty. If basal cells and basal membrane are intact after surgery, the recovery of nasal mucosa takes 5 days after trauma. If all nasal mucosa layers are damaged mechanically, it takes 1 week for stratified epithelium to regenerate, 3 weeks for formation of new ciliary cells, and at the end of 6th week for total recovery. 45 For this reason, we waited for full recovery of nasal mucosa and evaluated postoperative nasal MCC times at the 3rd month of control. CONCLUSION In this study it was detected that nasal septal deviation and smoking deteriorates nasal MCC time and this result can be seen easily with the saccharine test. The saccharine test is a reliable, easy, and harmless method for measuring nasal MCC time. We showed that properly performed septoplasty surgery decreases nasal MCC time during the late postoperative period, but MCC times are still longer than normal. REFERENCES 1. Stanley PJ, Wilson R, Greenstone MA, et al. Effect of cigarette smoking on nasal mucociliary clearance and ciliary beat frequency. Thorax 41: , Waguespack R. Mucociliary clearance patterns following endoscopic sinus surgery. Laryngoscope 105:1 40, Sisson JH, Yonkers AJ, and Waldman RH. Effects of guaifenesin on nasal mucociliary clearance and ciliary beat frequency in healthy volunteers. Chest 107: , Wullstein SR. Die Septumplastik bzw. submuköse Septumrezektion ohne postoperative Nasentamponade. HNO 27: , Uslu H, Uslu C, and Varoğlu E. Effects of septoplasty and septal deviation on nasal mucociliary clearance. Int J Clin Pract 58: , Lale AM, Mason JD, and Jones NS. Mucociliary transport and its assessment: A review. Clin Otolaryngol 23: , Scadding GK. Adverse effects of benzalkonium chloride on the nasal mucosa: Allergic rhinitis and rhinitis medicamentosa. Clin Ther 22: , Richards DH. Preservation of nasal sprays. J Allergy Clin Immunol 106: , Houtmeyers SE, Gosselink R, Gayan-Ramirez G, and Decramer M. Regulatıon of mucociliaray clearence in health and disease. Eur Respir J 13: , Bush A, Cole P, Hariri M, et al. Primary ciliary dysknesia: Diagnosis and standarts of care. Eur Respir J 12: , Tsang KW, Rutman A, Kanthakumar K, et al. Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics. Am J Respir Crit Care Med 48: , Corbo MG, Foresi A, Bonfitto P, et al. Measurement of nasal mucociliary clearance. Arch Dis Child 64: , Deniz M, and Uslu C. Nasal mucocilliary clearance in total laryngectomized patients. Eur Arch Otorhinolaryngol 263: , Deitmer T. Physiology and pathology of the mucociliary system. Special regards to mucociliary transport in malignant lesions of the human larynx. Arch Otorhinolaryngol 43:1 136, Mercke U, Hakansson CH, and Toremalm NG. The influence of temperature and mucociliary activity. Acta Otolaryngol (Stockh) 78: , Dalhamn T. Mucus flow and ciliary activity in the trachea of healthy rats and rats exposed to respiratory irritant agents. Acta Physiol Scand 36(suppl):1231, Andersen I, Lundqvist B, and Proctor GE. Human response to 78-hour exposure to dry air. Arch Environ Health 29: , Wanner A. State of the art. Clinical aspects of mucociliary transport. Am Rev Respir Dis 116:73 125, Breuninger H. Über das physikalisch-chemische Verhalten des Nasenschleims. Arch Ohr Nas Kehlk-Heilkd 184: , Andersen I, Lundqvist B, Jensen PL, and Proctor GE. Human response to controlled levels of sulfur dioxide. Arch Environ Health 28:31 39, Asmundsson T, and Kilburn KH. In Sputum. Dulfano MJ (Ed). Springfield: Charles C. Thomas, 252: , Dalhamn T. The effect of cigarette smoke on ciliary activity in the upper respiratory tract. Arch Otolaryngol 70: , Wanner A, Hirsch JA, and Greneltch DE. Tracheal mucous velocity in beagles after chronic exposure to cigarette smoke. Arch Environ Health 27: , Reimer A, Von Mecklemburg C, and Toremalm NG. The mucociliary tract. III. A functional and morphologic study of humans and animals with special reference to maxillary sinus diseases. Acta Otolaryngol (Stockh) 12(suppl):335, Sakakura Y, Ukai K, Majima Y, et al. Nasal mucociliary clearance under various conditions. Acta Otolaryngol (Stockh) 96: , Maurizi M, Paludetti G, Todisco T, et al. Ciliary ultrastructure and nasal mucociliary clearance in chronic and allergic rhinitis. Rhinology 22: , Wanner A. Allergic mucociliary dysfunction. Laryngoscope 93:68 70, Maurizi M, Ottaviani F, Paludetti G, et al. Adenoid hypertrophy and nasal mucociliary clearance in children. A morphologic and functional study. Int J Pediatr Otorhinolaryngol 8:31 42, Sanchis J, Dolovich M, Eng P, et al. Pulmonary mucociliary clearance in cystic fibrosis. N Engl J Med 288: , Pavia D, Sutton PP, and Agnew JE. Measurement of bronchial mucociliary clearance. Eur J Respir Dis 64:127, Sackner MA. Mucociliary transport. Ann Otol 87: , Kensler GJ, Battista SP. Components of cigarette smoke with ciliary depressant activity. N Engl J Med 269: , Ballenger JJ. Experimental effect of cigarette smoke on human respiratory cilia. N Engl J Med 263: , Vastag E, Matthys H, Zsamboki G, et al. Mucociliary clearance in smokers. Eur J Respir Dis 68: , Satsuki A. Nasal mucociliary clearance of chronic sinusitis in relation to rheological properties of nasal mucus. Ann Otol Rhinol Laryngol 107:47 51, Del Donno M, Bittesnich D, Chetta A, et al. The effect of inflammation on mucociliary clearance in asthma: An overview. Chest 118: , Coromina J, and Sauret J. Nasal mucociliary clearance in patients with nasal polyposis. ORL J Otorhinolaryngol Relat Spec 52: , January February 2009, Vol. 23, No. 1

6 38. Ho JC, Chan KN, Hu WH, et al. The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. Am J Respir Cit Care Med 163: , Puchell E, Aug F, Pham QT, and Bertrand A. Comprasion of methods for measuring nasal mucociliary clearance in man. Acta Otolaryngol 91: , Mortensen J, Lange P, Jorgen N, and Groth S. Lung mucociliary clearance. Eur J Nucl Med 21: , Kao CH, Jiang RS, Wang SJ, and Yeh SH. Influence of age, gender and ethnicity on nasal mucociliary clearance function. Clin Nucl Med 19: , David B. The nasal septum. In Scott-Brown s Otolaryngology de. Alan GK (Ed). Butterworth-Heinemann: Oxford, , Ginzel A, and Illum P. Nasal mucociliary clearance in patients with septal deviation. Rhinology 18: , Shone GR, Yardley MP, and Knight LC. Mucociliary function in the early weeks after nasal surgery. Rhinology 28: , Ohashi Y, Nakai Y, Ikeoka H, and Furuya H. Regeneration of nasal mucosa following mechanical injury. Acta Otolaryngol Suppl 486: , e American Journal of Rhinology & Allergy 7

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