Nazla-i-muzmin (chronic rhinosinusitis) refers to the inflammation of the mucosal lining of nose and paranasal sinuses lasting for more than 12 weeks. The term sinusitis is replaced by rhinosinusitis because sinusitis often preceded by rhinitis and rarely occurs without concurrent nasal airway inflammation (Benninger, 2003). The repeated attacks of acute sinusitis lead to chronic sinusitis or acute sinusitis may lead to chronic sinus disease (Schlossberg, 1987). The bacteria or fungi are commonly associated with this disease. Clinically, it is very difficult to cure most cases in the stage when ciliary activity is impaired due to thickening and damage of the mucous membrane (Braunwald and Fauci, 2001). This condition may headway until the sinus is filled with polypi and pus which is allowed at frequent intervals into the nose. The discharge is frequently foul. Pain and tenderness may disappear as the condition is settled into chronic stage (Hall and Colman, 1981). Chronic sinusitis is a major health care issue that affects a large group of population. The prevalence of sinusitis in Southern countries like India 134,198,900 out of 1,065,070,607 populations (U.S census bureau, 2004). Roughly 12% of Americans beneath the age of 45 years report side effect of incessant sinusitis. (Adams and Marano, 1995) Around 40 million Americans are influenced by sinusitis consistently, with 33 million instances of interminable sinusitis revealed every year to the U.S communities for infection control and prevention (Hodgson and Cohen, 1999). When sinusitis is viewed as together with usually related comorbid conditions, for example, un-favourably susceptible rhinitis, asthma and constant bronchitis, worsening of these sicknesses influences in excess of 90 million individuals about one of three Americans (Mihail, 2009).

The current medical management includes the use of decongestants, antihistaminics and antibiotics but they do not cure all the patients. The surgical intervention e.g antral puncture and drainage is also recommended as a therapeutic approach which fails to provide permanent cure to all patients. The Unani medicines have been used to treat chronic rhino-sinusitis since ages. They have been found safe and effective in its management. But there is a lack of documentary evidence to prove its efficacy in terms of clinical study. Keeping in view the given circumstances, this study was designed to evaluate the safety and efficacy of the classical Unani formulation containing the ingredients Shoniz (Nigella sativa), Zaranbad (Curcuma zedoaria), Bisbasa (Myristica fragrans), Asal (honey). (Anonymous, YNM). The outcome of this study could be utilized to generate documentary evidence of effectiveness of the Unani formulation in clinical practice.

This study was carried out with 60 participants (30 participants in each group) diagnosed with chronic rhinosinusitis at outdoor patient department of National Research Institute of Unani Medicine for skin disorders (NRIUM-SD) Hyderabad during 1st July 2019 and 30th July 2020. The protocol of the study was approved by the institutional ethics committee (38-18/2018-19/CRIUM/Tech/IEC-10/12) and registered in Clinical Trials Registry-India(CTRI) under registration no. CTRI/2019/04/018668 before enrolment of the first participants. This study was designed as a randomized, controlled, parallel group and open label clinical study. The participants aged between 18 years to 65 years of either sex were included in this study based on the symptoms such as rhinorrhoea, sneezing, facial pain, nasal discharge, and nasal blockage. The participants having comorbid conditions such as diabetes mellitus, hypertension, pregnancy, immunosuppressed participants, ischaemic heart disease and hepato-renal dysfunction were not included in this study.

The demographic characteristics at baseline of the participants is shown in Table 1. The baseline characteristics were comparable in both groups. In this study we enrolled 30 participants (63.3% female and 36.6% male) in each group. The average age (± SD) was 30.36 (± 10.20) years and 32.63 (± 10.97) years in the control and test group respectively. The maximum number of the participants was present in 18-27 years age group i.e., 13 participants (43%) in the control group versus 11 participants (36.6%) in the test group. Average chronicity of rhinosinusitis was 31.26 (± 39.01) months in the control group and 23.86 (± 43.46) months in the test group at the baseline. The haematological and biochemical parameters were remained within the normal limits at baseline as well as post treatment.

Table 2 shows the presence of the symptoms of chronic rhinosinusitis at baseline in the test and control groups. The sneezing was present in 29 participants (96.7%) in each test and control groups. Facial pain was found in 21 participants (70%) in the test group versus 23 participants (76.7%) in the control group. In the control group, 28 participants (93.3%) had loss of sense of smell whereas it was present in 21 participants (90%) in the test group. In the control group 26 participants (86.7%) reported cough in comparison to 20 participants (66.7%) in the test group. The post nasal drip, thick nasal discharge, ear pain, nasal blockage and dizziness were reported in 29 participants (96%), 29 participants (96%), 17 participants (56.7%), 27 participants (90%) and 21 participants (70%) in the test group.

Improvement in the symptoms in terms of snot score has been summarised in Table 3. In the test group, the difference in snot score at post treatment comparing to the baseline of the symptoms rhinorrhoea, sneezing, facial pain, loss of sense of smell, cough, post nasal drip, thick nasal discharge, ear pain, nasal blockage and dizziness had been found clinically and statistically significant. On comparing inter-group, the difference in snot score at post treatment of the symptoms rhinorrhoea, sneezing, facial pain, loss of sense of smell, cough post nasal drip, thick nasal discharge, ear pain, nasal blockage and dizziness was not statistically significant.

Our study focused on clinical evaluation of efficacy and safety of a Unani formulation in management of chronic rhinosinusitis. It was observed that the majority of participants were female (63.3%) in each group corresponding to the study done by Seys SF (Seys and De Bont, 2020). The mean age of the participants was 32.63 (±10.97) years in the test group and 30.36 (±10.20) years in the control group. A previous study also showed the similar mean age of the participants (Dar and Lone, 2013). The majority of the participants were in the age group of 18-27 years. The similar findings was reported in an another study (Chaturvedi and Grewal, 2020). In this study family history of chronic rhinosinusitis was present in 36.7% participants and 30% participants in the test and control groups respectively. Our findings corresponds to the previously reported study (Chaturvedi and Grewal, 2020). It was observed that chronic rhinosinusitis was prevalent in 23.3% damvi (sanguine) participants followed by 43.4% participants balghami (phlegmatic), 23.3% participants safravi (bilious) and 10% participants sawdawi (melancholic) in the test group. On the contrary, the control group had 50% participants balghami followed by 10% participants safravi, 33.3% participants damvi and 6.7% participants saudawi temperaments. This observation correspond to the observation given by Unani physician who observed that chronic rhinosinusitis was a balghami disease. (Anonymous, YNM)

The efficacy of the formulation was assessed in terms of reduction in Snot score at post treatment comparing to baseline in each group. This study demonstrated that the difference in mean Snot score in test group and control group were 2.1 and 2.0 comparing with baseline. The difference in mean Snot score was statistically significant in both the groups. The result of this study revealed that Unani formulation was comparatively more effective clinically than that of control drug. The magnitude of reduction in Snot score was comparatively higher in the test group. The Unani formulation had shown encouraging results in terms of reduction in Snot score after treatment of 21 days.

The Unani formulation had been found effective in alleviating signs and symptoms of chronic rhinosinusitis in this study. Its possible mechanism of action may be explained in terms of pharmacological properties of the ingredients of the Unani formulation. The Unani formulation used as a test drug in this study contained four ingredients (i.e, Nigella sativa, Curcuma zedoaria, Myristica fragrans and Honey). Shoniz (Nigella sativa) is a known anti-inflammatory (Anonymous, 2007), concoctive (Munshi, 2007) expectorant (Kabīruddīn, YNM) deobstruent (Shamshuddin, 2008) and analgesic (Anonymous, 2007) medicine. It may help in reducing inflammation of nasal mucosa and expulsion of accumulated secretions. It also possess anti-bacterial (Ahmad and Ghafoor, 2004) and anti-fungal (Bita and Rosu, 2012) properties. Moreover, Zaranbad (Curcuma zedoaria) is another ingredient of the Unani formulation and used as deobstruent (Baitar, 1999) and expectorant (Hakeem, 2002). It may facilitate excretion of accumulated secretions from the paranasal sinuses. Bisbasa (Myristica fragrans) possess anti-inflammatory activity. A study revealed that the methanol extract of Myristica fragrans (1.5g/kg), ether fraction (0.9g/kg) and n-hexane fraction (0.5g/kg) had anti-inflammatory activity similar to that of indomethacin (10mg/kg). The phytochemical myristicin was responsible for the anti-inflammatory activity (Ozaki and Soedigdo, 1989). Honey is a potent laxative and deobstruent. (Hakeem, 2002) It may help in excretion of viscid phlegm accumulated in paranasal sinuses. Its antibacterial properties controlled the growth of microorganisms in the sinuses as a result facial heaviness, nasal obstruction, nasal irritation and postnasal drip may got improved.

The Unani formulation was found safe and tolerable. All biochemical and haematological parameters remained within normal limits when compared from the baseline value with that of post treatment. There are certain limitations in this study. The sample size was small. The duration of protocol therapy was very short. The time period and financial funding were very limited. Although the study was designed to minimize the biases and effect of confounder (if any), the outcome of the study could have biases due to not implementation of blinding in the study due to differences in physical features of the test and control drugs. It may be suggested that another rigorous clinical study may be conducted to further establish its effectiveness and safety in larger population.

The outcome of this study suggests that this Unani classical formulation may be recommended for the management of chronic rhinosinusitis. Although this formulation had been used as a therapeutics for chronic rhinosinusitis since a long time, the outcome of this study validates its effectiveness in the treatment of chronic rhinosinusitis. Nowadays there is an emerging demand regarding scientific evidence of effectiveness of the pharmacopoeial and classical Unani formulations. The outcome of this study could be utilized to carry out another study with large sample size to establish the effectiveness of this Unani formulation in the management of chronic rhinosinusitis.