Nasal mucociliary clearance in obstructive sleep apnea syndrome patients Mahmut Deniz, M.D.,1 Erdogan Gultekin, M.D.,1 Zafer Ciftci, M.D.,1 Recep Alp, M.D.,2 Damla Nihan Ozdemir, M.D.,1 Aklime Isik, M.D.,1 and Oral Burak Demirel, M.D.1

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ABSTRACT

Background: The main objective of this study was to investigate the correlation between the level of mucociliary dysfunction and severity of obstructive sleep apnea syndrome (OSAS). The effect of smoking in OSAS patients on mucociliary dysfunction was also assessed. Methods: It is a descriptive study that compares variables between groups (univariate analysis). In this clinical trial 122 patients with varying degrees of OSAS and 49 healthy volunteers were included (n ⫽ 171). Patients were divided into three groups as having mild, moderate, and severe OSAS, according to their apnea hypopnea index (AHI) values. (AHI values are typically categorized as 5–15/hr, mild OSAS; 15–30/hr, moderate OSAS; and ⬎30/hr, severe OSAS.) The control group was comprised of healthy subjects. Each group was divided into smoking and nonsmoking subgroups. The mucociliary rates of the subjects were measured using the saccharin test. Statistical analysis was performed with the GraphPad Prism Version 3 pocket program. Results: Mild and moderate OSAS groups showed similar results with control group (p ⫽ 0.869), but severe OSAS patients showed a statistically significant difference with control group (Kruskal–Wallis [KW] ⫽ 32.28; p ⫽ 0.0032 and p ⬍ 0.05). Although in the moderate OSAS group the mucociliary clearance rates showed a tendency to decrease, this decrease was not significant (p ⫽ 0.453). A statistically significant difference was observed between smokers and nonsmokers in terms of mucociliary clearance times in all groups (KW ⫽ 18.24; p ⫽ 0.001). Conclusion: The nasal mucociliary system is significantly deteriorated in severe OSAS patients and they should be meticulously observed to prevent sinonasal infections. Measures to enhance mucociliary activity in these patients should be taken. Smoking, a well-known inhibitor of mucociliary activity, also has a negative impact on the mucociliary function of OSAS patients and quitting smoking would be of benefit for these patients. (Am J Rhinol Allergy 28, e178 –e180, 2014; doi: 10.2500/ajra.2014.28.4094)

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he mucociliary system is one of the most important and indispensable mechanisms protecting the airway against ambient microorganisms, foreign particles, and noxious substances. It has a delicate mechanism of action with a high tendency to entrap and remove particles.1 Removal of foreign particles from the respiratory tract requires effective ciliary activity and regular regeneration of airway fluids lining the moist surface of the respiratory mucosa. Many chronic medical conditions may have detrimental effects on mucociliary transport.2,3 Mucociliary clearance rate may be measured by various methods and the saccharin test is frequently used for this purpose. Normal saccharin clearance time is 9–17 minutes, and values higher than 20 are assumed to be pathological.4 The obstruction of the upper airway was found to be associated with a decrease in mucociliary clearance rate.2,3 Obstructive sleep apnea (OSA) is a relatively common entity with an incidence of 2–4%.5 Clinically, OSA syndrome (OSAS) is defined by the occurrence of daytime sleepiness, loud snoring, witnessed breathing interruptions, or awakenings due to gasping or choking. These findings should be accompanied by at least five obstructive respiratory events (apneas, hypopneas, or respiratory effort-related arousals) per hour of sleep.6,7 Effects of nasal continuous positive airway pressure (nCPAP) in OSAS patients on nasal mucociliary were extensively studied by many studies. However, in the literature, there are only a few studies investigating the association between OSAS and mucociliary dysfunction. We aimed to discuss our findings under the scope of the literature regarding this association in this study. To provide additional information to the literature, we measured the mucociliary clearance rates in OSAS patients and compared our findings with the results of healthy control subjects. The main objec-

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From the 1Department of Otorhinolaryngology and 2Department of Neurology, Namık Kemal University, Tekirdag, Turkey The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Mahmut Deniz, M.D., Namık Kemal University, 100 yıl mah., Tekirdag˘, 59000, Turkey E-mail address: [email protected] Copyright © 2014, OceanSide Publications, Inc., U.S.A.

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tive of this study was to investigate the correlation between the level of mucociliary dysfunction and severity of obstructive sleep apnea syndrome (OSAS). The effect of smoking in OSAS patients on mucociliary dysfunction was also assessed.

MATERIALS AND METHODS It is a descriptive study that compares variables between groups (univariate analysis). This clinical trial was performed in a tertiary referral center, Namık Kemal University Hospital, between April 2013 and September 2013. The permission of the local Ethics Committee was given and all patients filled out an informed consent form. Polysomnography tests were performed at the Department of Neurology in the same hospital. One hundred twenty-two patients who had OSAS and 49 healthy volunteer subjects were included. Patients were divided into three groups as having mild, moderate, and severe OSAS, according to their apnea hypopnea index (AHI) values. (AHI values are typically categorized as 5–15/hr, mild OSAS; 15–30/hr, moderate OSAS; and ⬎30/hr, severe OSAS.) Each group was also divided into smoking and nonsmoking subgroups (Table 1). All subjects enrolled in our study underwent rigorous subjective and objective evaluation. Physical examinations of the subjects were performed using a 0° rod telescope by the same examiner and all pathological findings were recorded. In addition, paranasal sinus computerized tomography scans of all subjects were taken and data were obtained and recorded. In the Department of Neurology, all subjects including controls underwent polysomnographic analysis. The control group was comprised of healthy individuals who had no history or symptoms of OSAS. Patients using nCPAP mask or presenting with a history of recent upper respiratory tract infection were not included in the study. Any subjects with nasal septal deviation, nasal polyps, chronic sinusitis, adenoid vegetation, and allergic rhinitis were excluded from this study. The mucociliary rates of the subjects were measured using the saccharin test. Although the saccharin test has limitations, many investigators used the saccharin test in their studies because it is not harmful to human beings, not invasive, easy to use, and cheap. The test was performed at room temperature while patients were in a sitting position with their heads tilted upward. After the nasal secre-

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moderate OSAS group the mucociliary clearance rates showed a tendency to decrease, this decrease was not significant (p ⫽ 0.453). The nasal mucociliary clearance time average was found to be 12.27 ⫾ 3.28 minutes for the mild OSAS patients, 14.21 ⫾ 2.07 minutes for the moderate OSAS patients, 28.26 ⫾ 4.01 minutes for the severe OSAS patients (p ⬍ 0.05), and 12,18 ⫾ 4.24 minutes for the control group (Table 2). Between the mean values of the mucociliary clearance times of the nonsmokers and smokers groups we observed a statistically significant difference. In the mild OSAS group, smokers showed 13.25 ⫾ 2.2 minutes and nonsmokers showed 12.01 ⫾ 1.14 minutes of mucociliary clearance time (p ⫽ 0.046). In the moderate group, smokers showed 15.16 ⫾ 1.1 minutes and nonsmokers showed 13.15 ⫾ 1.3 minutes of mucociliary clearance time (p ⫽ 0.028). In the severe OSAS group, smokers showed 30.29 ⫾ 2.7 minutes and nonsmokers showed 27.12 ⫾ 3.2 minutes of mucociliary clearance time (p ⫽ 0.036). In the control group, smokers showed 14.21 ⫾ 2.4 minutes and nonsmokers showed 11.03 ⫾ 2.19 minutes of mucociliary clearance time (p ⫽ 0.014; Table 3). Among all of the groups smokers have the highest mucociliary clearance time (KW ⫽ 18.24; p ⬍ 0.05; Fig. 2).

Table 1 Groups regarding sex and smoking presence in OSAS patients and control group

Male Female Smokers Nonsmokers Total

Mild OSAS

Moderate OSAS

Severe OSAS

Control Group

21 (56.7%) 16 (43.3%) 11 (29.7%) 26 (70.3%) 37 (100%)

22 (53.6%) 19 (46.4%) 8 (19.5%) 33 (80.5%) 41 (100%)

26 (59%) 18 (41%) 16 (36.3%) 28 (63.7%) 44 (100%)

26 (53.1%) 23 (46.9%) 5 (10.2%) 44 (89.8%) 49 (100%)

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The four groups were similar for demographic parameters (␹2-test ⫽ 1.24; p ⫽ 0.482). OSAS ⫽ obstructive sleep apnea syndrome.

mucociliary clearance me (minutes) 28.26 (p0.05) 12.27(p>0.05)

12.18

DISCUSSION

severe OSAS

The relationship between obstructed nasal passages and sleepdisordered breathing has been studied for over 30 years; nasal mucosal changes were found in the obstructed side and many medications were used, but their ability to successfully treat OSA has not been established.9–11 OSAS presents with symptoms of upper airway obstruction. It is characterized by a collapse of the pharyngeal airway resulting in repeated episodes of airflow cessation, oxygen desaturation, and sleep disruption.12 There are many studies investigating the effects of nCPAP treatment on the nasal mucociliary activity in OSAS patients. Saka13 reported that despite the occurrence of some structural changes in the nasal mucosa, mucociliary transport time—an indicator of nasal function—seems to be unaffected from CPAP treatment. Constantinidis14 stated that dry and cold air might cause excretion of various mediators that lead to changes in the mucus and these alterations in the epithelial level might affect the mucociliary transport. Hilding15 noted that although the goblet cell population increased and ciliated epithelium decreased in the obstructed side, the other side displayed thickening of respiratory mucosa and multistratified fat epithelial cells. De Oliviera16 reported that there was no significant change in the mucociliary transport time of patients having nCPAP treatment. However, the effects of OSAS on the nasal airway have not been extensively studied. In the literature, only a few studies are available but they have limitations in subgroups of OSAS. Schro¨der et al. reported that in untreated OSAS patients atrophic epithelium is common whereas ciliated epithelial types are rare,17 but authors did not subgroup OSAS patients according to the severity such as mild, moderate, or severe OSAS. Passali et al. reported that the mucociliary clearance of mild and moderate OSAS patients were deteriorated,18 but they did not study severe OSAS patients. Therefore, we decided to make a comprehensive study of OSAS patients with subgroups. In our study, we investigated the mucociliary clearance rates in OSAS patients and compared our findings with the results of healthy control subjects. Mild and moderate OSAS groups showed similar results with the control group (p ⬎ 0.05), but the severe OSAS group showed a statistically significant difference when compared with the control group (p ⬍ 0.05). Average mucociliary clearance time in the severe OSAS group was significantly higher than in the control group. Severity and prolongation of obstruction results with oxygen desaturation of nasal mucosal tissues, which may lead to ultrastructural changes and deterioration of mucociliary clearance in severe OSAS patients. Implications of our findings will provide additional information to the literature.

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0 mild OSAS

moderate OSAS

severe OSAS control group

Figure 1. Mean values of the mucociliary clearance times (in severe obstructive sleep apnea syndrome [OSAS], p ⫽ 0.0032, p ⬍ 0.05).

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tions were cleaned, a saccharine tablet with dimensions of 1 ⫻ 1 ⫻ 1 mm3 was placed 1 cm posterior to the anterior border of the inner surface of each nasal cavity. The patients were warned not to sneeze or to tilt their heads downward. They were instructed to swallow once in every 30 seconds and inform the physician as soon as they perceive the taste of saccharin in their mouth. The moment most close to the instant of report of taste was addressed as the mucociliary transport time.8 Statistical analysis was performed with the GraphPad Prism Version 3 pocket program (GraphPad Software Inc., San Diego, CA). While comparing the groups, the Kruskal–Wallis (KW) test was used. Regarding the presence of smoking and sex distribution, nonparametric tests were used. A Tukey multiple comparison test was used to compare the subgroups. For comparing the double groups Mann– Whitney U test was used, and for comparing the qualitative data, ␹2-tests was used. Results were considered as significant at the value of p ⬍ 0.05.

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RESULTS

We included 122 OSAS patients who had polysomnography reports and 49 healthy volunteer subjects (total, 171 individuals whose age ranged from 25 to 64 years [mean age, 46.3 years]). Of these, 76 were female and 95 were male subjects. Mean age for mild, moderate, severe OSAS groups, and control groups was 41.72 ⫾ 13.2 years, 43.25 ⫾ 11.8 years, 46.56 ⫾ 15.4 years, and 42.61 ⫾ 14.6 years old, respectively. The four groups were similar for demographic parameters (␹2 ⫽ 1.24; p ⫽ 0.482). Mean values of the mucociliary clearance times showed differences in groups. Mild and moderate OSAS groups showed similar results with the control group (p ⫽ 0.869 and p ⬎ 0.05) but severe OSAS patients showed a statistically significant difference with the control group (KW ⫽ 32.28; p ⫽ 0.0032 and p ⬍ 0.05; Fig. 1). Although in the

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moderate OSAS

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Table 2 The mean values of mucociliary clearance time in the groups (min)

MCC time

Mild OSAS

Moderate OSAS

Severe OSAS

Control Group

12.27 ⫾ 3.28

14.21 ⫾ 2.07

28.26 ⫾ 4.01

12,18 ⫾ 4.24

Statistically significant difference was observed between severe OSAS and control groups (p ⫽ 0.0032; p ⬍ 0.05). OSAS ⫽ obstructive sleep apnea syndrome.

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Table 3 The mean values of mucociliary clearance time according to smoking (min)

Smoker Nonsmokers

Mild OSAS

Moderate OSAS

Severe OSAS

13.25 ⫾ 2.2 12.01 ⫾ 1.14

15.16 ⫾ 1.1 13.15 ⫾ 1.3

30.29 ⫾ 2.7 27.12 ⫾ 3.2

Statistically significant difference was observed between smokers and nonsmokers groups (KW test ⫽ 18.24; p ⬍ 0.05). OSAS ⫽ obstructive sleep apnea syndrome; KW ⫽ Kruskal–Wallis.

30,29 (p=0.036) 30

5.

27,12

25

6. 20 15,16 (p=0.028) 15

13,25(p=0.046) 12,01

13,15

14,21(p=0.014) 11,03

smokers

7.

non smokers

10

8.

0 mild OSAS

moderate OSAS severe OSAS

control Group

Figure 2. Mucociliary clearance time according to smoking (minutes; p ⬍ 0.05).

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Smoking is another factor that causes damage to the mucociliary clearance. Some studies showed the changes in viscoelasticity properties of mucous, and the ciliotoxic effects of smoking disturb the mucociliary clearance.19,20 Our study included smoking individuals in four groups. In all groups, the mucociliary clearance time averages of smoking groups are significantly higher than the nonsmokers (p ⬍ 0.05).

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CONCLUSION

The nasal mucociliary system is significantly deteriorated in severe OSAS patients and they should be meticulously observed to prevent sinonasal infections. Measures to enhance mucociliary activity in these patients should be taken. Smoking, a well-known inhibitor of mucociliary activity, also has a negative impact on the mucociliary function of OSAS patients and quitting smoking would be of benefit for these patients.

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15. 16.

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REFERENCES 1.

Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir Dis 116:73–125, 1977. 2. Uslu H, Uslu C, Varog˘lu E, et al. Effects of septoplasty and septal deviation on nasal mucociliary clearance. Int J Clin Pract 58:1108– 1111, 2004. 3. Gudis D, Zhao KQ, and Cohen NA. Acquired cilia dysfunction in chronic rhinosinusitis. Am J Rhinol Allergy 26:1–6, 2012. 4. Asai K, Haruna S, Otori N, et al. Saccharin test of maxillary sinus mucociliary function after endoscopic sinus surgery. Laryngoscope 110:117–122, 2000.

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19.

20.

14.21 ⫾ 2.4 11.03 ⫾ 2.19

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Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230– 1235, 1993. Friedman M, Ibrahim H, and Joseph NJ. Staging of obstructive sleep apnea/hypopnea syndrome: A guide to appropriate treatment. Laryngoscope 114:454–459, 2004. Aubert-Tulkens G, Hamoir M, Van den Eeckault J, and Rodenstein DO. Failure of tonsil and nose surgery in adults with long-standing severe pulmonary sleep apnea syndrome. Arch Intern Med 149:2118– 2121, 1989. Corbo GM, Foresi A, Bonfitto P, et al. Measurement of nasal mucociliary clearance. Arch Dis Child 64:546–550, 1989. Rombaux P, Liistro G, and Hamoir M. Nasal obstruction and its impact on sleep-related breathing disorders. Rhinology 43:242–250, 2005. Olsen KD, Kern EB, and Westbrook PR. Sleep and breathing disturbance secondary to nasal obstruction. Otolaryngol Head Neck Surg 89:804–810, 1981. Meen EK, and Chandra RK. The role of the nose in sleep-disordered breathing. Am J Rhinol Allergy 27:213–220, 2013. Epstein LJ, Kristo D, Strollo PJ Jr, et al.; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 5:263–276, 2009. Saka C, Alicura S, Akin I, et al. The effects of CPAP treatment on nasal mucosa in patients with obstructive sleep apnea. Eur Arch Otorhinolaryngol 269:2065–2067, 2012. Constantinidis J, Kno¨bber D, Steinhart H, et al. Fine-structural investigations of the effect of nCPAP-mask application on the nasal mucosa. Acta Otolaryngol 120:432–437, 2000. Hilding A. Experimental surgery of the nose and sinuses. Arch Otolaryngol 16:9–18, 1932. de Oliveira LR, Albertini Yagi CS, Figueiredo AC, et al. Short-term effects of nCPAP on nasal mucociliary clearance and mucus transportability in healthy subjects. Respir Med 100:183–185, 2006. Schro¨dter S, Biermann E, and Halata Z. Histologic evaluation of nasal epithelium of the middle turbinate in untreated OSAS patients and during nCPAP therapy. Rhinology 42:153–157, 2004. Passali FM, Bellussi L, Mazzone S, and Passali D. Predictive role of nasal functionality tests in the evaluation of patients before nocturnal polysomnographic recording. Acta Otorhinolaryngol Ital 31:103–108, 2011. Deniz M, Uslu C, Ogredik EA, et al. Nasal mucociliary clearance in total laryngectomized patients. Eur Arch Otorhinolaryngol 263:1099– 1104, 2006. Kensler GJ, and Battista SP. Components of cigarette smoke with ciliary depressant activity. N Engl J Med 269:1161–1166, 1963. e

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September–October 2014, Vol. 28, No. 5

Nasal mucociliary clearance in obstructive sleep apnea syndrome patients.

The main objective of this study was to investigate the correlation between the level of mucociliary dysfunction and severity of obstructive sleep apn...
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