Hostname: page-component-76fb5796d-x4r87 Total loading time: 0 Render date: 2024-04-25T20:54:32.783Z Has data issue: false hasContentIssue false
  • English
  • Français

Molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea

Published online by Cambridge University Press:  10 January 2022

C-C Lin Open the ORCID record for C-C Lin [Opens in a new window] ,
Y-P Wang ,
C-H Chiu ,
Y-K Sun ,
M-W Lin  and
I-S Tzeng
C-C Lin*
Affiliation:
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
Y-P Wang
Affiliation:
Department of Otolaryngology, Mackay Memorial Hospital, Taipei, Taiwan
C-H Chiu
Affiliation:
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
Y-K Sun
Affiliation:
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
M-W Lin
Affiliation:
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
I-S Tzeng
Affiliation:
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
*
Author for correspondence: Dr C-C Lin, Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Rd, Xindian District, New Taipei City 23142, Taiwan E-mail: cclinpro@yahoo.com Fax: +88 62 6628 9009
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.

Method

Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions.

Results

The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group.

Conclusion

Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

Keywords

Sleep Apnea, ObstructiveUvulaAirway RemodelingCytokinesInflammation
Type
Main Article
Information
The Journal of Laryngology & Otology , Volume 136 , Issue 11 , November 2022 , pp. 1096 - 1104
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Dr C-C Lin takes responsibility for the integrity of the content of the paper

References

White, DP. Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med 2005;172:1363–70CrossRefGoogle ScholarPubMed
Dempsey, JA, Veasey, SC, Morgan, BJ, O'Donnell, CP. Pathophysiology of sleep apnea. Physiol Rev 2010;90:47–112CrossRefGoogle ScholarPubMed
Yokoe, T, Minoguchi, K, Matsuo, H, Oda, N, Minoguchi, H, Yoshino, G et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 2003;107:1129–34CrossRefGoogle ScholarPubMed
Lavie, L. Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev 2003;7:35–51CrossRefGoogle ScholarPubMed
Almendros, I, Acerbi, I, Puig, F, Montserrat, JM, Navajas, D, Farré, R. Upper-airway inflammation triggered by vibration in a rat model of snoring. Sleep 2007;30:225–7CrossRefGoogle Scholar
Schwarz, EI, Martinez-Lozano Sinues, P, Bregy, L, Gaisl, T, Garcia Gomez, D et al. Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea. Thorax 2016;71:110–17CrossRefGoogle ScholarPubMed
Woodson, BT, Garancis, JC, Toohill, RJ. Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 1991;101:1318–22CrossRefGoogle ScholarPubMed
Paulsen, FP, Steven, P, Tsokos, M, Jungmann, K, Müller, A, Verse, T et al. Upper airway epithelial structural changes in obstructive sleep-disordered breathing. Am J Respir Crit Care Med 2002;166:501–9CrossRefGoogle ScholarPubMed
Sekosan, M, Zakkar, M, Wenig, BL, Olopade, CO, Rubinstein, I. Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 1996;106:1018–20CrossRefGoogle ScholarPubMed
Hamans, EP, Van Marck, EA, De Backer, WA, Creten, W, Van de Heyning, PH. Morphometric analysis of the uvula in patients with sleep-related breathing disorders. Eur Arch Otorhinolaryngol 2000;257:232–6CrossRefGoogle ScholarPubMed
Hunter, JA, McVittie, E, Comaish, JS. Light and electron microscopic studies of physical injury to the skin. II. Friction. Br J Dermatol 1974;90:491–9CrossRefGoogle Scholar
Tobin, MJ. Sleep-disordered breathing, control of breathing, respiratory muscles, and pulmonary function testing in AJRCCM 2001. Am J Respir Crit Care Med 2002;165:584–97CrossRefGoogle ScholarPubMed
Friberg, D, Gazelius, B, Hökfelt, T, Nordlander, B. Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers. Regul Pept 1997;71:29–36CrossRefGoogle ScholarPubMed
Berger, G, Gilbey, P, Hammel, I, Ophir, D. Histopathology of the uvula and the soft palate in patients with mild, moderate, and severe obstructive sleep apnea. Laryngoscope 2002;112:357–63CrossRefGoogle ScholarPubMed
Carrera, M, Barbé, F, Sauleda, J, Tomás, M, Gómez, C, Agustí, AG. Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure. Am J Respir Crit Care Med 1999;159:1960–6CrossRefGoogle ScholarPubMed
Berger, G, Finkelstein, Y, Ophir, D. Histopathologic changes of the soft palate after laser-assisted uvulopalatoplasty. Arch Otolaryngol Head Neck Surg 1999;125:786–90CrossRefGoogle ScholarPubMed
Sériès, F, Côté, C, St Pierre, S. Dysfunctional mechanical coupling of upper airway tissues in sleep apnea syndrome. Am J Respir Crit Care Med 1999;159:1551–5CrossRefGoogle ScholarPubMed
Iber, C, Ancoli-Israel, S, Chesson, AL, Quan, SF. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology, and Technical Specifications. American Academy of Sleep Medicine, 1st edn. Westchester, IL: American Academy of Sleep Medicine, 2007Google Scholar
Johns, MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–5CrossRefGoogle ScholarPubMed
Carpagnano, GE, Spanevello, A, Sabato, R, Depalo, A, Turchiarelli, V, Foschino Barbaro, MP. Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome. Transl Res 2008;151:45–50CrossRefGoogle ScholarPubMed
Carpagnano, GE, Spanevello, A, Sabato, R, Depalo, A, Palladino, GP, Bergantino, L et al. Systemic and airway inflammation in sleep apnea and obesity: the role of ICAM-1 and IL-8. Transl Res 2010;155:35–43CrossRefGoogle ScholarPubMed
Sariman, N, Levent, E, Aksungar, FB, Soylu, AC, Bektaş, O. Homocysteine levels and echocardiographic findings in obstructive sleep apnea syndrome. Respiration 2010;79:38–45CrossRefGoogle ScholarPubMed
Wasicko, MJ, Hutt, DA, Parisi, RA, Neubauer, JA, Mezrich, R, Edelman, NH. The role of vascular tone in the control of upper airway collapsibility. Am Rev Respir Dis 1990;141:1569–77CrossRefGoogle ScholarPubMed
Boyd, JH, Petrof, BJ, Hamid, Q, Fraser, R, Kimoff, RJ. Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med 2004;170:541–6CrossRefGoogle ScholarPubMed
Loubaki, L, Jacques, E, Semlali, A, Biardel, S, Chakir, J, Sériès, F. Tumor necrosis factor-alpha expression in uvular tissues differs between snorers and apneic patients. Chest 2008;134:911–18CrossRefGoogle ScholarPubMed
Sériès, F, Chakir, J, Boivin, D. Influence of weight and sleep apnea status on immunologic and structural features of the uvula. Am J Respir Crit Care Med 2004;170:1114–19CrossRefGoogle ScholarPubMed
Kimoff, RJ, Hamid, Q, Divangahi, M, Hussain, S, Bao, W, Naor, N et al. Increased upper airway cytokines and oxidative stress in severe obstructive sleep apnoea. Eur Respir J 2011;38:89–97CrossRefGoogle ScholarPubMed
Hatipoğlu, U, Rubinstein, I. Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 2003;70:665–71CrossRefGoogle ScholarPubMed
Kataoka, T, Enomoto, F, Kim, R, Yokoi, H, Fujimori, M, Sakai, Y et al. The effect of surgical treatment of obstructive sleep apnea syndrome on the plasma TNF-alpha levels. Tohoku J Exp Med 2004;204:267–72CrossRefGoogle ScholarPubMed
Stimpson, P, Kotecha, B. Histopathological and ultrastructural effects of cutting radiofrequency energy on palatal soft tissues: a prospective study. Eur Arch Otorhinolaryngol 2011;268:1829–36CrossRefGoogle ScholarPubMed