TITLE: Role of 

  ABSTRACT:
Dushta Pratishyaya is the chronic stage of Pratishyaya, which occurs due to neglect or improper management of the disease Pratishyaya. In modern science, chronic sinusitis can be correlated with Dushta Pratishyaya on the basis of the signs, symptoms, complications, and prognosis. Changing lifestyles, rapid urbanization, and the increase in cases of antibiotic resistance are responsible for the rise in the prevalence of sinusitis. In the present clinical study, 37 patients were registered and were randomly divided into three groups: A, B, and C; of the 37 patients, 31 completed the full course of treatment. In group A, Trayodashanga Kwatha with Madhu was given orally; in group B, Pradhamana Nasya with Trikatu + Triphala Churna was administered; and in group C (combined group), Pradhamana Nasya was administered initially, followed by oral Trayodashanga Kwatha with Madhu. In group A, complete relief was observed in 10% of the patients; in group B, marked improvement was observed in 81.82% of patients; and in group C, marked relief was observed in 60% of patients. In comparison to other groups (Group A and Group B), Group C showed percentage wise better results in most of the symptoms.

BODY.INTRODUCTION:
Acharya Sushruta, while dealing with the diseases of the nose, devoted a separate chapter to Pratishyaya after explaining Nasagata Roga in detail.[1] This fact itself shows that Pratishyaya has been a major problem since ancient times.  Dushta Pratishyaya has not been mentioned as a separate disease but, rather, is considered to be the complication of different types of Pratishyaya.[1] As Dushta Pratishyaya is a serious and complicated condition, it is very difficult to treat. It can cause many complications, such as Badhirya, Andhata, Ghrananasha, etc.[2]  In general, the features of the disease Dushta Pratishyaya are similar to that of chronic sinusitis in modern science. Both these diseases are characterized by nasal blockage, nasal discharge, headache, anosmia, heaviness in the head, etc.[3]  As the nose is in direct contact with the external environment, it is exposed to the many microorganisms and pollutants present in the atmosphere. Due to the increase in environmental pollution and the busy lifestyles of today, rhinitis is a common disease in the present era.[4] Improper management of this stage leads to sinusitis, which may later lead to chronic sinusitis.[3] More than 120 million Indians suffer from at least one episode of sinusitis each year[4] and, according to the American Academy of Otolaryngology and Head and Neck Surgery, more than 37 million Americans suffer from at least one episode of sinusitis each year.[5] Jamnagar is a coastal city with many industries. Due to the air pollution, respiratory infections are common. A large number of patients with sinusitis also report to the ENT – Shalakya, OPD of IPGT and RA.  Once the sinuses are infected, improper management and poor dietary habits can lead the disease into a chronic phase.[3] This chronic sinusitis is too difficult to drain out completely. It remains as a focus of infection, leading to inflammation in all associated structures, e.g., the tonsils, ear, pharynx, larynx etc.[6] Ultimately, it may lead to complications such as otitis media, orbital cellulitis, osteomylitis, etc.[7] In modern medical science, a wide range of antibiotics and decongestants are available for the treatment of sinusitis.[8] But these drugs can help only in the initial stage. Once pus collection forms in the sinuses and is not drained spontaneously, only surgical intervention can help.[7] After drainage of the sinuses, antibiotics can help. FESS (functional endoscopic sinus surgery), Caldwell-Luc operation, Howarth's operation, etc., are the chief operative procedures to drain the sinus if conservative measures fail.[3] These surgical procedures are associated with many complications, including bleeding, oro-antral fistula, infraorbital anaesthesia, neuralgia, and paraesthesia.[7] The modern treatment modalities for chronic sinusitis are also expensive and not free from side effects. Also, frequent use of antibiotics leads to the gradual development of drug resistance. Moreover, no drug for treatment of allergy and viral infection is available in the modern science.  Acharya Sushruta has not clearly mentioned the line of treatment of Dushta Pratishyaya. The treatment advised by Vagbhattacharya for Dushta Pratishyaya is similar to that for Rajayakshma and Krimi Roga.[9] Among the various treatment modalities, Nasya is the chief procedure to drain Doshas from Shirah.[9]  Considering all these facts, we carried out this clinical trial to find out the best treatment protocol for the management of the Dushta Pratishyaya. As Dushta Pratishyaya is chronic stage of the Pratishyaya and Kapha Dosha is predominant in this condition, Pradhamana Nasya was selected as the chief Shodhana procedure in this study. Trikatu + Triphala Churna for Pradhamananasya[10] and Trayodashanga Kwatha[11] were selected. In the combination of Trikatu + Triphala Churna, Triphala neutralizes the Tikshnata of Trikatu and thus makes it easier for the patient to it. The main ingredient of Trayodashanga Kwatha is Dashamula and it is Shothahara, Rasayana, and Tridoshashamaka.[1213]  For assessment of the results, we evaluated the subjective improvement in clinical features and, in addition, as an objective parameter, we measured C-reactive protein (CRP) levels, which is a biomarker of inflammation.

BODY.AIMS AND OBJECTIVES:

To assess the role of Trikatu + Triphala Churna for Pradhamana Nasya in Dushta PratishyayaTo assess the role of Trayodashanga Kwatha in Dushta PratishyayaTo assess the combined effect of Pradhamana Nasya and Shamana Aushadhi in Dushta Pratishyaya.


BODY.MATERIALS AND METHODS.SELECTION OF PATIENTS:
Subjects for the study were selected from among the patients attending the OPD/IPD of the Department of Shalakya, Institute for Post Graduate Teaching & Research in Ayurveda, Gujarat Ayurved University, Jamnagar. We used simple random sampling for selecting the subjects for the study.  Inclusion criteria: Patients having signs and symptoms of Dushta Pratishyaya (chronic sinusitis) and between the ages of 8 years and 80 years were selected for the study.  Exclusion criteria: Patients below 7 years and above 80 years; those having history of hypertension or diabetes mellitus; those with any chronic debilitating infectious disease; those with any inflammatory disease; and those requiring surgical treatment (e.g., for nasal polyp) were excluded from the study.  A proforma was prepared for data collection, incorporating all the relevant points from the point of view of both Ayurveda and modern medicine.  The trial drugs were prepared in the pharmacy of Gujarat Ayurved University.

BODY.MATERIALS AND METHODS.ETHICAL CLEARANCE:
The study protocol was cleared by the ethical committee of the Institute. Written consent was taken from each patient for participation in the study. Patients were free to withdraw from the study at any time without giving any reason.

BODY.MATERIALS AND METHODS.INVESTIGATIONS:

Hematological examination: Total white blood cell count, differential count, erythrocyte sedimentation rate, hemoglobin, and absolute eosinophil count were checked; other investigations were done, if required.Urine examination: Routine and microscopic examinationRadiological examination of paranasal sinusesDiagnostic nasal endoscopyC-reactive protein test (CRP test)[14]


BODY.MATERIALS AND METHODS.GROUPING:

Group A (Shamana Chikitsa)Trayodashanga Kwatha orallyDose: 45 ml (approx) twice dailyDuration: 45 daysSahapana: Madhu[15]Group B (Shodhana Chikitsa)Pradhamana Nasya with Trikatu + Triphala ChurnaLavana Siddha Tila Taila in Purva Karma for Sthanika Abhyanga[16]Dose for Pradhamana Nasya: 1–3 Muchchuti (250–750 mg)Duration: Pradhamana Nasya was given for a maximum seven sittings, with an interval of 1 day between each sitting.[17]Group C (combined group): Shodhana + Shamana ChikitsaPradhamana Nasya was given as described in group B. After completion of seven sittings of Nasya, Trayodashanga Kwatha with Madhu was given orally for 45 days.
  Follow-up: All patients were asked to come for follow-up every 7 days for 1 month.

BODY.MATERIALS AND METHODS.CRITERIA FOR ASSESSMENT:
The assessment was done by evaluating the changes in the signs and symptoms after treatment with the help of a suitable scoring method by giving score in the range 0 to 4. Changes in the value of CRP were also noted.

BODY.MATERIALS AND METHODS.OVERALL EFFECT OF THERAPY:

Cured: 100% relief in signs and symptoms and no recurrence during the follow-up periodMarked improvement: 76%–99% relief in signs and symptomsModerate improvement: 51%–75% relief in signs and symptomsMild improvement: 26%–50% relief in signs and symptomsUnchanged: Up to 25% reduction in signs and symptoms was noted as unchanged


BODY.MATERIALS AND METHODS.STATISTICAL ANALYSIS:
The information, gathered on the basis of observations was subjected to statistical analysis and Student's paired 't' test was applied. For comparison between two therapies, Student's unpaired 't' test was applied. The results were interpreted at P<.05, P<.01, and P<.001 significance levels.

BODY.OBSERVATIONS:
The study was conducted on 37 patients who were randomly allotted into three groups.    In the present study, the majority of the patients, i.e., 43.24%, were in the age-group of 21–30 years; 54.05% were females; 40.54% were doing house work; 72.97% were from polluted surrounding; 94.59% had the history of taking allopathic treatment; 100% were taking Viruddhashana; 45.94% were having Vata Kapha Deha Prakriti. Among the patients, 56.75% had turbinate hypertrophy, 45.94% had congestion of the nasal mucosa, 67.56% had deviated nasal septum, 62.16% had watery nasal discharge, and 21.62% had purulent nasal discharge. On examination, there was swelling over the right maxillary sinus in 5.40% of the patients and over the left maxillary sinus in 8.10% of the patients. There was tenderness on palpation over the left frontal sinus in 43.24% of patients, over the right frontal sinus in 40.54%, over both maxillary sinuses in 35.13%, over the left ethmoidal sinus in 21.62%, and over the right ethmoidal sinus in 16.21%. X-ray PNS showed haziness in the right frontal sinus in 86.48%, in the left frontal sinus in 72.97%, in the right maxillary sinus in 81.08%, in the left maxillary sinus in 67.56%, and in both ethmoidal sinuses in 8.10% of the patients. All the patients (100%) in the study had Nasasrava (nasal discharge) as the chief complaint. Postnasal drip and Nasavarodha (nasal blockage) were observed in 97.29% of the patients. Shirahshula (headache), Shirogaurava (heaviness in head), and Swarabheda (change of voice) were observed in 91.89%, 78.37%, and 70.27% of the patients, respectively. Kshavathu (sneezing) was observed in 67.56% of the patients, Ghranaviplava (loss of smell) in 64.86%, Mukhadaurgandhya (halitosis) in 59.45%, Kasa (cough) in 45.94%, Aruchi (anorexia) in 40.54%, and Jwara (fever) in 27.02% of the patients.  In present study most of the patients (97.29%) were taking Sheetambu, followed by 64.86% who were taking AtiGuru Ahara, and 59.45% Vishamashana. The Aharaja Nidanas are a reflection of the changing and busy lifestyles of today and play a role in the pathogenesis of the disease.  The data of Viharaja Nidana reveals that all the patients showed increase of symptoms in Ritu Vaishamya and Ritu Sandhi, whereas Raja Sevana was found in 78.37% and Dhuma Sevana in 72.97% of the patients. Here, Ritu Vaishamya and Ritu Sandhi are such etiological factors which are very difficult to avoid and Raja-Dhuma Sevana are also very difficult to avoid all the time for all persons and these etiological factors are described as Sadyojanak Nidan for Pratishyaya by Acharya Sushruta. These observations reveal that the area of this study is prone to atmospheric pollution. Chronic contact with such unavoidable Hetus will nullify the effect of the therapy. This could be the reason why patients were not getting relief even after taking treatment for many years.  Krodha as Manasika Nidana was observed in the maximum numbers of the patients (67.56%). It is also reflection of the Prakriti of the patients and also today's lifestyles. This also plays major role in the pathogenesis of the disease.  In Kasa, group B showed better results. This may be due to the sudden reduction of postnasal drip due to the treatment. In Mukhadaurgandhya also, group B showed better results, which suggests that Pradhamana Nasya is very effective for removing Dushta Kapha quickly.  When we used Student's unpaired 't' test to compare the results in the combined group with that in the Trayodashanga Kwatha group, there is no statistically significant difference between the groups in the relief obtained in any of the symptoms. However, on analyzing the percentage of relief obtained, combined therapy gives better results in Shirahshula, postnasal drip, Shirogaurava, Kasa, Aruchi, and Mukha Daurgandhya than does Trayodashanga Kwatha alone.  On comparing the Group C (Combine therapy) with Group B (Pradhamana Nasya), Group C showed better (highly significant) results in Kasa and Mukha Daurgandhya and significantly better results in postnasal discharge. In other symptoms like Nasasrava, Shirogaurav and Aruchi, symptom wise Group C showed better results than Group B but the difference is statistically insignificant.  Better results in the Sarvadehika Lakshanas were also seen in the combined group. the combined group also showed less recurrence of the symptoms after completion of treatment as compared to the other two groups. This may be due to an immunomodulatory property of the drug. Recurrence was more common in group B than in the other groups. This may be due to incomplete Shodhana. While Nasya will relieve the local pathology, the general vitiation of Doshas and Agni is not dealt with efficiently; hence, though rapid symptomatic relief may be seen after Nasya, recurrence can occur.  The variations in the results also depend upon the chronicity of the disease, effect of the weather, and the Bala of the individuals. It also depends upon the Bhishagvashyata of the patients.

BODY.RESULTS.EFFECT OF THERAPY ON SYMPTOMS:
Group A showed better results than the other groups in Nasasrava (100%), Kshavathu (100%), and Swarabheda (100%). Group B showed better results than the other groups in Shirahshula (100%), Kasa (100%), and Mukhadaurgandhya (91.66%). Group C showed better results than the other groups in postnasal drip (PND) (85.71%), Shirogaurava (94.73%), and Aruchi (100%) [Table 1].   Table 1 Effect of therapy on symptoms   In Nasavarodha, groups A and B showed almost equal results, i.e., 95% and 95.83%, respectively. Groups A and B showed equal results in Ghranaviplava (100%). All three groups showed equal results in Jwara (100%).

BODY.RESULTS.EFFECT OF THERAPY ON X-RAY FINDINGS:
In opacity of sinuses, group A showed statistically highly significant result in both maxillary and right frontal sinuses, group B showed highly significant result in both maxillary and frontal sinuses and group C showed highly significant results in both frontal sinuses. In ethmoid sinuses, percentage wise group A showed better results than group C but the results are statistically insignificant [Table 2].   Table 2 Effect of therapy on X-ray findings 

BODY.RESULTS.EFFECT OF THERAPY ON TENDERNESS OVER SINUSES:
Though percentage wise Group A and Group C showed better result in comparison to Group B in tenderness on Frontal, maxillary and ethmoid sinuses, the results are insignificant, whereas result of Group B in Frontal sinuses are highly significant and in maxillary sinuses are significant [Table 3].   Table 3 Effect of therapy on tenderness over the sinuses 

BODY.RESULTS.EFFECT OF THERAPY ON HEMATOLOGICAL VALUES:
The total leucocyte count was reduced by 12.44% in group C. Reduction of absolute eosinophil count was by 12.69% in group C and by 1.78% in group B. Erythrocyte sedimentation rate (ESR) decreased by 27.5% in group B and by 6.66% in group A; the ESR increased by 35.02% in group C. CRP was decreased by 71.25% in group C, by 42.56% in group A, and by 1.91% in group B. In this study, a total 13 (41.94%) patients in the three groups showed increase in the CRP after treatment (as compared to the values before treatment) though in all cases the increased values were almost within normal range. All these patients, however, had symptomatic relief. The increase in CRP was more common in group B (Pradhamana Nasya) and was elevated beyond the normal range in some patients. Possibly, the oral drug (Trayodashanga Kwatha) given in the other two groups (Group A and Group C) has an anti-inflammatory action and benefit of this drug was not available to the patients in group B; that may be the reason for increase of CRP level more in patients of Group B [Table 4].   Table 4 Effect of therapy on hematological values   The changes in hematological values are statistically nonsignificant but all patients had good relief in symptoms. Probably the time period was short for changes to be seen; further studies with longer duration of treatment may provide the answer.

BODY.RESULTS.TOTAL EFFECT OF THERAPY:
In group A, complete relief was observed in 10% of the patients, marked relief in 70% of the patients, and moderate relief in 20% of the patients. In group B, marked improvement was observed in 81.82% of the patients and moderate improvement was observed in 18.18% of the patients. In group C, marked relief was observed in 60% of the patients, moderate relief in 30% of the patients, and mild relief in 10% of the patients.

BODY.DISCUSSION.SELECTION OF THE PROBLEM:
Changing lifestyles, increased pollution, rapid urbanization, and increase in resistance to antibiotics are responsible for the increased prevalence of upper respiratory tract infections. The incidence of upper respiratory tract infection is very high in India. The most common problem related to upper respiratory tract is Pratishyaya or rhinitis which in the later stage converts into Dushta Pratishyaya or chronic sinusitis. In modern medical science, a wide range of effective antibiotics and decongestants are available. But these drugs can help only in the initial stage; if pus collection forms in the sinuses and does not drain spontaneously only surgical intervention can help. After drainage of the sinuses, antibiotics can help. The surgical procedures may themselves lead to complications. The modern medical treatment modalities for chronic sinusitis are expensive and not free from side effects. Also, frequent use of antibiotics leads to the development of drug resistance. Moreover, no effective drug for allergy and viral infection is available in the modern science.  Hence, we felt the need to derive a treatment protocol that would help drain the sinuses, remove the pathology, and promote immunity.

BODY.DISCUSSION.SELECTION OF DRUG:
The main treatment for accumulated Doshas in Dushta Pratishyaya is Shodhana Nasya. Hence, Pradhamana Nasya, which is the best among all the Shodhana Nasya, was selected for this study. Acharya Charaka has advised a combination of Trikatu and Triphala Churna for Pradhamana Nasya in the context of Pratishyaya Chikitsa. Trikatu has Katu Rasa, Laghu and Tikshna Guna, Katu Vipaka, Ushna Veerya, Vata-Kaphashamaka, Shothahara, Sroto Shodhana, Vatanulomana, Lekhana, Kaphanissaraka, Shleshmahara, anti-inflammatory, antibacterial, antirhinoviral, and immunostimulatory properties.[18] Triphala has Ruksha Guna and Tridoshashamaka as well as Sroto Shodhana, Shothahara, Vatanulomana, Kaphanissaraka, antibacterial, anti-inflammatory, and immunomodulatory properties.[18] All these properties of Trikatu + Triphala Churna Yoga help to remove the pathology and promote local immunity. Thus, Trikatu + Triphala Churna was selected for Pradhamana Nasya in the present study.  For Abhyanga in Purva Karma of Nasya, Saindhava Taila was selected which is described by Acharya Sushruta in the context of Shwasaroga Chikitsa. Saindhava and Tila Taila have Snigdha Guna and Tridoshashamaka properties[18] Saindhava also has Sukshmasrotogami properties[19] by which it reaches the minute channels. Hence, Saindhava Taila was selected for Abhyanga as the Purvakarma of Pradhamana Nasya in the present study. Swedana Karma (which is also done in Purva Karma) causes liquefecation of the accumulated Doshas especially vitiated Kapha.  Acharya Vagbhatta has stated that Dushta Pratishyaya should be treated similar to Yakshma. Thus, Trayodashanga Kwatha was selected here, which is mentioned in Bhaishajya Ratnavali in the context of Rajayaksma. Trayodashanga Kwatha includes Dashamula, Shunthi, Pippali, and Dhanyaka. Most of the ingredients of this Yoga have Katu, Tikta, Kashaya Rasa; Laghu, Ruksha, Tikshna Guna; Katu Vipaka; Ushna Veerya; Deepana, Pachana, Shothahara, Sroto Shodhana, Kaphaghna, Jwarahara, Vatanulomana, Shulaprashamana properties. It also has antimicrobial, anti-inflammatory and immunostimulatory property.[20] Dashamoola is also accepted as Shothahara Kashaya by Acharya Charak. Hence Trayodashanga Kwatha can be used to manage Dushta Pratishyaya. Because of having all these properties it causes Sampraprti Vighatana and treats the disease.  Again sinusitis is the inflammation of sinus mucosa and Acharya Charaka has accepted Dashamula as Shothahara Kashaya. In this context Trayodashanga Kwatha is also indicated in Pratishyaya.  In this study, Madhu (honey) was selected for the Sahapana of Trayodashanga Kwatha. Acharya Sharangadhara has advised Madhu as Sahapana in Kashaya in Vata Kaphaja Vikara. Also By the virtue of Laghu, Ruksha Guna; Katu Vipaka; Tridoshashamaka; Lekhanakaraka, Chhedana, Yogavahi, and Sukshmamarganusari properties[21] Madhu directly acts on the Vikrita Kapha besides being a vehicle for the Aushadhi Dravya.

BODY.OBSERVATIONS.MODE OF ACTION OF :
In Purva Karma of Nasya, Abhyanga and Swedana is done. Abhyanga causes Mruduta of Doshas and Swedana causes Vilayana (liquification) of accumulated Doshas. In the language of modern science, Abhyanga and Swedana increases the local blood supply and Swedana also liquefies the mucous. Due to vasodilatation the permeability of blood vessels increases, which makes the drug absorption faster.  In Pradhana Karma, the drug in Churna form is administered into the nostrils through Pradhamana Nadiyantra in the head-low position of the patient. Thus, the drugs reach the Shringataka and from there, through different Siras, it spreads to other parts like Netra, Shirah, etc. and removes the morbid Doshas.[22] By the properties of drug, it causes Srotoshuddhi and makes the Anulomana Gati of Vayu (mitigation of Vayu), which is hampered in Dushta Pratishyaya.  In Pashchata Karma, Urdhvanga massage and Swedana helps to drain out the Doshas and Swedana also causes Srotomukhavishodhana.  In addition, the drug compound has Srotoshodhana, anti-inflammatory, antibacterial, etc., properties, which help to treat the disease.  Most of the ingredients in Trayodashanga Kwatha are Katu, Tikta Rasa Pradhan; Laghu, Ruksha, Tikshna Guna Pradhana and having Ushna Veerya, Katu Vipaka; Vatanulomana, Shothahara, and Srotoshodhana properties. All these properties are very useful to remove the Srotorodha and promote the expulsion of vitiated Kapha from the sinuses. The Deepana and Pachana properties of Trayodashanga Kwatha cause Amapachana. By Amapachana and also Dhatvagnideepana, the Sara Dhatus are formed properly (Samyaka), which increases the Vyadhikshamatva (immunity). Vedanasthapana, Kasahara, Kanthya, etc., properties provide symptomatic relief. The anti-inflammatory properties of the ingredients reduce the inflammatory process in the nose and paranasal sinuses. The antibacterial activity arrests secondary infection and prevents recurrence of the disease.

BODY.CONCLUSION:
Each of the three groups showed better results relative to the other two in different symptoms. In comparison to other groups (Group A and Group B), Group C showed percentage wise better results in most of the symptoms.  The recurrence rate in the combined group was significantly lower than in the other groups. Better results in the Sarvadehika Lakshanas were also seen in the combined group. For good and long-lasting results Shodhana or Shamana therapy alone will not be adequate. A combination of Shodhana and Shamana therapy will yield better and longer lasting effects.

Question: Compared to Pradhamana Nasya +l Trayodashanga Kwatha + Madhu what was the result of Pradhamana Nasya + Trikatu + Triphala Churna on Tenderness on frontal sinus?
Evidence: In ethmoid sinuses, percentage wise group A showed better results than group C but the results are statistically insignificant
Answer: no significant difference