Auris Nasus Larynx 41 (2014) 269–272

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Topical Nigella Sativa for nasal symptoms in elderly Cagatay Oysu a, Ahmet Tosun a, Huseyin Baki Yilmaz b, Asli Sahin-Yilmaz a,*, Deniz Korkmaz a, Ahmet Karaaslan a a b

Umraniye Education and Research Hospital, Department of Otolaryngology, Istanbul, Turkey Tuzla State Hospital, Otolaryngology Clinic, Istanbul, Turkey

A R T I C L E I N F O

A B S T R A C T

Article history: Received 15 May 2013 Accepted 9 December 2013 Available online 4 January 2014

Objective: To compare the effects of intranasal application of black seed (Nigella Sativa) oil (NSO) and isotonic sodium chloride solution (ISCS) on nasal symptoms of the elderly. Methods: In this prospective, crossover randomized controlled trial, 42 geriatric patients with nasal dryness and related symptoms were randomized to receive either 2 weeks of isotonic sodium chloride solution (ISCS) followed by 2 weeks of N. sativa oil (NG oil) or the same treatment in the opposite order. There was a washout period of 3 weeks in between the treatment periods. Subjective symptoms including nasal dryness, burning, obstruction, itching and crusting were evaluated by a visual analog scale. Mucociliary function was evaluated with saccharin test. Results: Nasal dryness, obstruction and crusting improved significantly with the use of NSO compared to ISCS without any evidence of relevant carryover effects (p < 0.05 for all for the difference in treatment). There was no significant difference between the effect of NSO and ISCS on nasal burning and itching (p > 0.05 for all). There was no change in mucociliary clearance during any of the treatment periods. Conclusion: NSO is a better alternative to ISCS to treat nasal mucosa symptoms due to aging. ß 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Nigella Sativa oil Nasal dryness Black seed oil

1. Introduction Cold and dry weather conditions cause nasal dryness and related symptoms such as stuffiness, itching, crusting, burning and pain in many people. These symptoms get worse when the humidity is low especially in air-conditioned rooms and during long journeys by airplane [1]. The elder population is more prone to these symptoms due to the effects of aging on the nose including hormonal and mucosal changes [2,3]. The traditional manner to treat dry nasal mucosa has been to administer isotonic sodium chloride solution (ISCS). As an alternative, some seed extracts such as sesame oil has been used in treatment of dry nasal mucosa and was shown to be more effective than ISCS [1]. It is well-known that sesame oil contains tocopherol, and might neutralize oxidants such as ozone and oxides of nitrogen in the inhaled air and prevent tissue damage and inflammation [1]. Black seed or Nigella Sativa (NS), which is a dicotyledon of the Ranunculaceae family, has been employed for thousands of years as a spice, food preservative and traditional remediation [4]. Intranasal usage of NS was first stated in early Islamic resources

* Corresponding author. Tel.: +905334641479. E-mail address: [email protected] (A. Sahin-Yilmaz). 0385-8146/$ – see front matter ß 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.12.002

[5]. NS oil (NSO) contains tocopherol as high as the sesame oil. Kalus et al. [6] treated 152 patients with allergic rhinitis and asthma with high dose of NSO and observed a significant decrease in their symptoms. Although oral use of NSO has beneficial effect on symptoms in nasal diseases, there are no studies on topical use of NSO in remediation of nasal symptoms. The purpose of this study is to investigate the effects of topical use of NSO on symptoms of nasal dryness, stuffiness, itching, crusting and burning related to aging. 2. Material and methods 2.1. Study design This study was prospective, randomized, and crossover in design. After a primary clinical evaluation and nasal endoscopy, eligible subjects were randomized according to a computer generated randomization list. Allocation was concealed for patients and the investigators. Subjects were randomly allocated to receive either 2 weeks of N. sativa oil (NSO) followed by 2 weeks of isotonic sodium chloride solution (ISCS) or the same treatment in the opposite order. There was a washout period of 3 weeks in between the treatment periods. Both NSO and ISCS were administered with three sprays in each nostril 3 times daily and presented to the subjects as active therapies. Each patient was

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Fig. 1. Study protocol.

evaluated for their subjective VAS scores and mucociliary clearance for 4 times, at the beginning and the final day of the treatment with both NSO and ISCS. Study protocol is outlined in Fig. 1. 2.2. Subjects The study was approved by the Institiutional Review Board of our hospital. Informed consent was taken from all subjects. Patients were recruited from our outpatient clinic. The inclusion criteria included (a) subjects older than 55 years, (b) had symptoms of nasal dryness, burning, obstruction, itching and crusting for at least 3 months. Subjects with ongoing upper respiratory tract infections, present symptoms of allergic rhinitis, unilateral symptoms and marked deviation of the nasal septum, and those undergoing treatment with nasal steroids, nasal decongestants, or antiallergic medication were excluded. 2.3. Test products The products used in the study included a nasal spray containing cold press N. sativa oil (Origo Food Industries, Gaziantep Turkey; Turkish Ministry of Agriculture approval 13.07.2005#270587-6-00) reserved in 10 ml medical glass bottle, sealed with a dosage pump (one spray included 22.6 mg of N. sativa oil in 25 ml per nostril). The other product was a nasal spray with ISCS containing 0.9% sodium chloride in an identical 10 ml medical glass bottle sealed with a dosage pump. 2.4. Criteria for evaluation Mucociliary clearance was evaluated with saccharin test. Saccharin transit time was measured by placing a saccharin particle (Sakarin 20 mg, Mu¨nir S¸ahin I˙lac¸ Sanayi; Istanbul, Turkey) on the anterior inferior portion of the inferior turbinate. Patients were told to inform the tester after tasting saccharin. The transit time was measured in minutes. Each subject was evaluated for the efficacy of the treatment by using a standard visual analogue scale (VAS) ranging from 0 to (no symptoms) to 100 (the most severe symptoms) to assess the subjective symptoms including nasal dryness, stuffiness, crusting, itching and burning with or without pain.

2.5. Statistical analysis The number of subjects required for the study was determined according to standard power calculations. We determined the number of subjects needed to provide 80% power for detecting a difference between the two drugs by the use of a two-sided p value of 0.05). 3.2. Subjective symptoms At the initiation of the study, no statistically significant difference was demonstrated between the mean visual analog scales for any of the sinonasal symptoms (nasal dryness, burning, obstruction, itching and crusting) between the two treatment groups. Table 2 summarizes the comparison of scores on the visual analog scale for the study participants. Analysis of symptoms one by one has revealed that dryness, obstruction and crusting improved significantly with the use of NSO compared to ISCS

Table 1 Effect of ISCS (Isotonic Sodium Chloride Solution) and NSO (Nigella Sativa Oil) treatment on nasal mucociliary clearance. Data (minutes) in cells present mean  standard deviation. (t1–4) refers to time points shown in Fig. 1. Group 1 (NSO/ISCS)

Mucociliary Clearance

Group 2 (ISCS/NSO)

Before NSO (t1)

After NSO (t2)

Before ISCS (t3)

After ISCS (t4)

Before ISCS (t1)

After ISCS (t2)

Before NSO (t3)

After NSO (t4)

p value for carryover effect

p value for difference in treatment

14.48  7.61

10.38  5.47

13.24  6.03

11.95  5.33

14.57  8.17

13.62  9.72

12.95  6.09

9.76  3.22

0.60

0.07

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Table 2 Subjective evaluation of ISCS (Isotonic Sodium Chloride Solution) and NSO (Nigella Sativa Oil) treatment. Data in cells present mean  standard deviation. (t1–4) refers to time points shown in Fig. 1. Group I (NSO/ISCS)

Dryness Burning Obstruction Itching Crusting

Group II (ISCS/NSO)

Before NSO (t1)

After NSO (t2)

Before ISCS (t3)

After ISCS (t4)

Before ISCS (t1)

After ISCS (t2)

Before NSO (t3)

After NSO (t4)

p Value for Carryover effect

p Value for Difference in treatment

65.71  22.16 48.46  15.61 60.71  13.78 50.00  11.55 51.25  16.91

28.57  15.52 30.00  12.40 27.14  12.78 25.56  14.99 22.50  20.46

40.00  14.39 38.46  15.61 40.00  15.12 41.11  18.53 45.56  23.62

33.33  16.43 32.31  21.18 30.71  14.86 43.33  20.55 36.67  23.57

64.52  20.70 42.06  21.63 53.61  24.93 52.50  25.62 52.00  18.33

43.57  19.71 38.53  20.99 40.28  19.18 40.31  21.25 42.50  25.96

61.43  18.33 41.18  19.67 47.22  25.12 44.38  25.24 42.86  24.91

48.57  22.31 36.76  21.07 36.94  20.49 34.69  18.33 32.86  21.19

0.242 0.109 0.599 0.396 0.193

0.022 0.087 0.039 0.083 0.010

without any evidence of relevant carryover effects (p < 0.05 for all for the difference in treatment). No statistically significant difference was demonstrated between the effect of NSO and ISCS on nasal burning and itching (p > 0.05 for all). 3.3. Adverse effects Two patients complained of the taste and odor of the NSO; however, they have not stopped continuing the drug. 4. Discussion Nasal dryness, burning, obstruction, itching and crusting are common complaints among the elderly and can be attributed to age-related changes in nasal physiology and structure [8]. With aging, lymphatic tissue of the nasal mucosa is gradually replaced by connective tissue, resulting in fibrosis, which disrupts the secretory function of the mucosa. The end result is the atrophy of the glands and excretory ducts. Hollender showed decreased production of nasal mucus at people over the age of 50 [2]. He determined that excretory ducts of the glands were surrounded by hyaline tissue limiting their excreting function. These changes may resemble atrophic rhinitis, which also is characterized by fibrosis of the mucosa [2]. Internal factors such as menopause also contribute to mucosal deterioration [3]. Toppozada studied postmenopausal subjects and showed that, although the nasal mucosa remains normal, the number of goblet cells decrease, resilient structures atrophy and the basement membrane gets thicker with aging [3]. These histological changes probably cause nasal irritation, itching, dehydrated mucous and crusts occurring in the elderly [1]. Dry weather conditions and wide spread use of airconditioning aggravate nasal complaints in the elderly population [1]. The common management of nasal dryness and related symptoms has been to administer isotonic sodium chloride solution intranasally. However, its effectiveness is controversial. Seed extracts such as sesame oil have been proposed to be more effective [1]. The potential mechanism of the action of pure sesame oil has been attributed to its scavenger effects due to its high tocopherol content [1]. Tocopherols might neutralize oxidants such as ozone and oxides of nitrogen in the inhaled air and prevent tissue damage and inflammation that would otherwise occur [1]. The tocopherol content of NSO is comparable to that of the sesame oil. Furthermore, NS contains four kinds of oil, i.e., thymoquinone, carvacol, tanetol and 4-terpineol, which neutralize free radicals. Ample of evidence suggests that N. Sativa oil and thymoquinone, the main constituent of N. Sativa oil, have many gastroprotective effects. These effects have been postulated to be induced at least partly by their radical scavenging activity. Thymoquinone has also been shown to inhibit proton pump, acid secretion and neutrophil infiltration, while enhancing mucin

secretion, and nitric oxide production in the gastric mucosa [9] Thymoquinone has antibacterial, antioxidant, antiinflammatory, antihistaminic, cytoprotective and antineoplastic effects which have been shown in clinical and animal experiments [10–12]. NSO has also been shown to be a beneficial agent in protecting against ionizing radiation-related tissue injury of the tongue in rats [13] Kalus et al. used NSO enterally in patients with allergic rhinitis and found that complaints related to allergic rhinitis decreased significantly. In this report, 80% of the cases had improvement of allergic rhinitis symptoms compared to those who received placebo [6]. Topical medications are widely used in patients suffering from symptoms of the geriatric nose. Beside their pharmacological properties, these medications may have some physico-chemical characteristics that can alter nasal physiology. Osmolarity and tonicity are known to affect ciliary beat frequency; however, little is known about the effects of saline and nonsaline solutions on ciliary activity of nasal epithelial cells. Isotonic and hypotonic solutions have been shown not to produce any ciliary slowing [14]. Some essential oils (sesame oil, soy oil, peanut oil, lavender oil, eucalyptus oil, and menthol), tested at a concentration of 0.2% has been shown to increase the ciliary beat frequency measured by digital high-speed imaging [15]. Because of the chemical composition of NSO and encouraging results of in vivo studies, we assumed that NSO may be useful in treatment of nasal symptoms due to aging. We designed a cross over study so each of our subjects serve as his/her own control, thus avoiding problems of comparability of study. The current study failed to demonstrate objective improvement in the nasal mucociliary clearance of the elderly following the use of NSO. On the other hand, severity of nasal dryness, nasal obstruction and crusting significantly improved following fourteen days of NSO. One limitation of our study is that the ideal design would be a ‘‘double blind cross over design’’; however, we failed to accomplish this goal. In spite of the fact that two product bottles were identical in appearance, NSO and ISCS did have discernible difference in taste, smell or appearance. We doubt the blinding was effective, however one should accept that it is often impossible in these circumstances. Two patients complained of the taste and odor of the NSO; however, they have not stopped continuing the drug. Since the NSO used in this study was cold press, we believe that the use of pharmaceutical quality refined oil may improve patient compliance. In brief, our study suggests that the NSO can be a useful remedy to treat nasal mucosa symptoms due to aging. It is particularly useful for nasal dryness, obstruction and crusting related to aging. Symptomatic relief following NSO use is significantly better than ISCS. It can be used on demand, following a short term regular administration. Further histological studies are required regarding the effects of NSO on nasal mucosa.

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[9] Magdy MA, Hanan el-A, Nabila el-M. Thymoquinone: novel gastroprotective mechanisms. Eur J Pharmacol Dec 2012;15:697. [10] Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 2006;80:217–24. [11] Ragheb A, Attia A, Eldin WS, Elbarbry F, Gazarin S, Shoker A. The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury: a review. Saudi J Kidney Dis Transpl 2009;20:741–52. [12] Erdurmus M, Yagci R, Yilmaz B, Hepsen IF, Turkmen C, Aydin B, et al. Inhibitory effects of topical thymoquinone on corneal neovascularization. Cornea 2007;26:715–9. [13] Ustu¨n K, Taysı S, Sezer U, Demir E, Baysal E, Demir T, Sarıc¸ic¸ek E, Alkıs¸ H, Senyurt S, Tarakc¸ıog˘lu M, Aksoy N. Radio-protective effects of Nigella sativa oil on oxidative stress in tongue tissue of rats. Oral Dis 2013. Feb 11. [14] Min YG, Lee KS, Yun JB, Rhee CS, Rhyoo C, Koh YY, Yi WJ, Park KS. Hypertonic saline decreases ciliary movement in human nasal epithelium in vitro. Otolaryngol Head Neck Surg 2001;124:313–6. [15] Neher A, Gsto¨ttner M, Thaurer M, Augustijns P, Reinelt M, Schobersberger W. Influence of essential and fatty oils on ciliary beat frequency of human nasal epithelial cells. Am J Rhinol 2008;22:130–4.

Topical Nigella Sativa for nasal symptoms in elderly.

To compare the effects of intranasal application of black seed (Nigella Sativa) oil (NSO) and isotonic sodium chloride solution (ISCS) on nasal sympto...
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