Table of Contents

    Topic review

    Nasal Injury

    View times: 264
    Submitted by: Yogeswaran Lokanathan


    In this entry, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality.

    1. Introduction

    Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries.

    2. Complementary and Alternative Management

    Management of nasal injury has been described in many cultural and religious records in the past. Due to the intimate relationship between the nasal mucosa and the external environment through the air that is breathed in, herbal medicine plays a large role in the management of the many nasal injury occurrences within different cultures[1].

    2.1. Nasal Irrigation

    The ancient Hindu practice of Ayurveda provides the earliest record of nasal irrigation[2]. The Ayurvedic scriptures list out a number of personal hygiene practices termed soucha. Among the Soucha, there is jala neti, also known as the practice of nasal irrigation[3]. According to the scripture, a higher state of meditation can be achieved by purifying the nose as clear breathing can lead to clear thinking. The simplest method of nasal cleansing was to sniff water from cupped hands and blow it out, which is also a step in the Muslim ablutions practice[2]. In modern science, data from RCT has demonstrated the importance of nasal irrigation in enhancing the wound healing of the nasal mucosa[4].

    The precise mechanisms are still unknown but most experts think that it is due to the direct cleansing of the nasal mucosa, independent of the solution composition used[3]. This causes the mucus lining to be soft and dislodge. Furthermore, antigen and inflammatory mediators such as leukotrienes and prostaglandins that cause allergic reactions and can be removed by nasal irrigation. The composition of salt solutions can affect the effectiveness of nasal irrigation where the use of a lower concentration of salt and isotonic solutions will immediately reduce the microbial antigens significantly. On the other hand, it is shown that hypertonic solutions that are used can minimally influence the concentration of the microbial antigens.

    Nasal irrigation with the addition of ions such as sodium and chloride can promote the integrity and function of epithelial cells. Moreover, the addition of magnesium will reduce eicosanoid metabolism by directly inhibiting the 5-lipoxygenase enzyme, encouraging cell repair, and limiting inflammation[4]. Magnesium also inhibits exocytosis of permeabilized eosinophils and reduces respiratory cells apoptosis in association with zinc[4].

    2.2. Chinese Medicine

    In Chinese medicine, herbal formulations are created to balance the “Yin-Yang”, which is based on traditional Chinese medicine (TCM) theory. The occurrence of diseases is thought to be the result of imbalance within the theory. In Asian countries such as China, nasal steroids and oral antibiotics are used along with herbs as an adjuvant treatment for post-ESS care. A study was done to investigate the safety and effectiveness of Zhu-Yuan decoction (ZYD) in the postoperative care of patients for FESS. In TCM theory, ZYD is used to treat Chinese medicine symptoms (phlegm and heat obstructing the sinus). The study has shown that ZYD administration has produced significant results that have similar safety and efficacy as intranasal cortisone. However, the study was short-term (lasting 12 weeks) and required the study of long-term effects and further study to elucidate the underlying mechanisms of ZYD[5].

    2.3. Bee Propolis

    Propolis is the material used by bees to build their hives. Synthesized by bees from plant resin, it has been demonstrated to have anti-inflammatory activity[6]. A study with rat models and nasal injury have revealed the reduction of inflammation and enhancement of healing of wounds of the nasal mucosa[7]. It has also been shown in a study that propolis reduces the severity of the inflammation and preserve both goblet cells and ciliary in nasal mucosa[7]. The exact mechanisms of nasal mucosa wound healing by propolis requires further study but its healing properties have been suggested to be due to its immune-stimulating effect where cytokine secretion capacity increases significantly during the treatment period in a time-dependent manner. Furthermore, propolis can stimulate a significant increase in ECM components during the initial phase of wound repair. Another study that looks into caffeic acid phenyl ester, a bioactive compound of propolis, has also revealed enhancement of wound healing in the nasal mucosa[8].

    2.4. Curcumin

    Among the spices, the medicinal properties of turmeric have been reported substantially[9]. In cutaneous wounds, curcumin has demonstrated anti-inflammatory and wound enhancement properties[10]. Utilizing the nasal injury rat model, curcumin has also been reported to reduce inflammation and enhance wound healing in the nasal mucosa[11]. This is due to a reduction of the inflammatory response in the nasal mucosa by inhibiting the cytokines production for the activation of macrophages and monocytes[11]. On the other hand, curcumin enhances the granulation tissue organization, which contains a higher number of smaller capillaries and myofibroblasts in a diabetic rat model[11].

    2.5. Stem Cell Therapy and Tissue Engineering

    Stem cells have been the subject of interest in regenerative medicine since the dawn of the 20th century. In terms of wound healing, there were reports on its efficacy with skin[12] and corneal epithelium[13] wound healing. Utilizing the nasal injury rabbit model, Kavuzlu et al. implanted adipose-derived mesenchymal stem cell sheet onto the nasal mucosa to enhance its healing[14]. The implant resulted in better morphology, abundance, and density of the ciliated nasal epithelial cells. The mechanisms regarding the healing process have been suggested to be due to increased re-epithelization and stimulation of wound angiogenesis through the secretion of growth factors, cytokines, and collagen tissue as well as antioxidant effect through neutralization of reactive oxygen species[14].

    Another study has attempted to utilize the aerosol delivery technique to deliver regenerative cells onto the injured tissue such as the works of Kardia and colleagues[15]. They successfully demonstrated an improvement of regeneration and repair in the respiratory tract of a rabbit upon delivery of aerosolized allogenic airway epithelial cells[15]. The regeneration and repair process involved rapid re-epithelialization of the denuded region where cell dedifferentiation, migration, proliferation, and re-differentiation occur for the repopulation of the tracheal epithelium. Furthermore, it has been suggested that the repair process is mediated by secretions of compounds such as growth factors, cytokines, and chemokines to induce tracheal epithelium repair[16].

    In many surgical interventions, autologous tissue graft is considered as the gold standard. This can be observed in burn wounds[17], ligament injury[18], and osteoarthritis[19]. The use of autologous nasal mucosa grafts on rabbit has shown to improve re-epithelization. Utilizing light and scanning electron microscopy, Topdag et al. had demonstrated that the ciliary epithelium covered greater area, had more mature and sophisticated cilia, and had less hypertrophied epithelium in grafted tissue compared to the non-grafted tissue[20].

    The entry is from 10.3390/ijms21020480


    1. Nasal injury;alternative therapy;stem cell
    2. Evelyn Y. Ho; Kathryn A. Cady; Jessica S. Robles; A Case Study of the Neti Pot’s Rise, Americanization, and Rupture as Integrative Medicine in U.S. Media Discourse. Health Communication 2016, 31, 1181-1192, 10.1080/10410236.2015.1047145.
    3. Rastogi, S.; Rastogi, R.; Rastogi, R.; Jalaneti application in acute rhino sinusitis‏. Indian J. Tradit. Knowl. 2007, 6, 324–327, .
    4. A.I. Giotakis; E.M. Karow; Marc Oliver Scheithauer; R. Weber; H. Riechelmann; Saline irrigations following sinus surgery - a controlled, single blinded, randomized trial. Rhinology journal 2016, 54, 302-310, 10.4193/rhin16.026.
    5. Jing Li; Chunquan Zheng; Hai Lin; Chen Yang; Siyuan Gu; Yi Wang; Honggang Duan; Effect of Zhu-yuan decoction in patients with chronic rhinosinusitis after functional endoscopic sinus surgery.. null 2018, 38, 83-88, .
    6. D. Henatsch; F. Wesseling; K. W. Kross; R. J. Stokroos; Honey and beehive products in otorhinolaryngology: a narrative review. Clinical Otolaryngology 2016, 41, 519-531, 10.1111/coa.12557.
    7. Mohammad Waheed El-Anwar; Said Abdelmonem; Ahmed A. Abdelsameea; Mohamed AlShawadfy; Kamal El Kashishy; The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study. International Archives of Otorhinolaryngology 2016, 20, 222-225, 10.1055/s-0036-1579664.
    8. Vefa Kınıs; Musa Ozbay; Mehmet Akdag; Ulas Alabalık; Aylin Gul; Beyhan Yılmaz; Hakan Özkan; Ismail Topcu; Vefa Kınış; Effects of caffeic acid phenethyl ester on wound healing of nasal mucosa in the rat: an experimental study. American Journal of Otolaryngology 2014, 35, 482-486, 10.1016/j.amjoto.2014.02.008.
    9. Shaveta Sood; Monika Nagpal; Role of curcumin in systemic and oral health: An overview. Journal of Natural Science, Biology and Medicine 2013, 4, 3-7, 10.4103/0976-9668.107253.
    10. Chandana Mohanty; Sanjeeb K. Sahoo; Curcumin and its topical formulations for wound healing applications. Drug Discovery Today 2017, 22, 1582-1592, 10.1016/j.drudis.2017.07.001.
    11. Gokhan Emiroglu; Zerrin Özergin Coşkun; Yildiray Kalkan; Ozlem Celebi Erdivanli; Levent Tumkaya; Suat Terzi; Abdulkadir Ozgur; Munir Demirci; Engin Dursun; The Effects of Curcumin on Wound Healing in a Rat Model of Nasal Mucosal Trauma. Evidence-Based Complementary and Alternative Medicine 2017, 2017, 1-6, 10.1155/2017/9452392.
    12. Yen-Chih Lin; Tara Grahovac; Sun Jung Oh; Matthew Ieraci; J. Peter Rubin; Kacey G. Marra; Evaluation of a multi-layer adipose-derived stem cell sheet in a full-thickness wound healing model. Acta Biomaterialia 2013, 9, 5243-5250, 10.1016/j.actbio.2012.09.028.
    13. Kohji Nishida; Masayuki Yamato; Yasutaka Hayashida; Katsuhiko Watanabe; Naoyuki Maeda; Hitoshi Watanabe; Kazuaki Yamamoto; Shigeru Nagai; Akihiko Kikuchi; Yasuo Tano; et al. Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface. Transplantation 2004, 77, 379-385, 10.1097/
    14. Ali Kavuzlu; Emel Çadallı Tatar; Tuğba Karagöz; Ferda Pinarli; Ilkan Tatar; Ömer Bayır; Mehmet Hakan Korkmaz; The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium. European Archives of Oto-Rhino-Laryngology 2017, 274, 3057-3064, 10.1007/s00405-017-4595-7.
    15. Egi Kardia; Ewe Seng Ch'ng; Badrul Hisham Yahaya; Aerosol‐based airway epithelial cell delivery improves airway regeneration and repair. Journal of Tissue Engineering and Regenerative Medicine 2017, 12, e995-e1007, 10.1002/term.2421.
    16. Egi Kardia; Rafeezul Mohamed; Badrul Hisham Yahaya; Stimulatory Secretions of Airway Epithelial Cells Accelerate Early Repair of Tracheal Epithelium. Scientific Reports 2017, 7, 11732, 10.1038/s41598-017-11992-6.
    17. Diana Kitala; Marek Kawecki; Agnieszka Klama-Baryła; Wojciech łabuś; Małgorzata Kraut; Justyna Glik; Ireneusz Ryszkiel; Mariusz Nowak; Allogeneic vs. Autologous Skin Grafts in the Therapy of Patients with Burn Injuries: A Restrospective, Open-label Clinical Study with Pair Matching. Advances in Clinical and Experimental Medicine 2016, 25, 923-929, 10.17219/acem/61961.
    18. Alec A. Macaulay; Dean C. Perfetti; William N. Levine; Anterior Cruciate Ligament Graft Choices. Sports Health: A Multidisciplinary Approach 2011, 4, 63-68, 10.1177/1941738111409890.
    19. Seán Flynn; Keir A. Ross; Charles P. Hannon; Youichi Yasui; Hunter Newman; Christopher D. Murawski; Timothy W. Deyer; Huong T. Do; John G. Kennedy; Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus. Foot & Ankle International 2015, 37, 363-372, 10.1177/1071100715620423.
    20. Shailendra Singh; Alistair Young; Clare-Ellen McNaught; The physiology of wound healing. Surgery (Oxford) 2017, 35, 473-477, 10.1016/j.mpsur.2017.06.004.