Efficacy of Pippali Rasayana as an Adjuvant Therapy on Pulmonary Function in Patients of Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic, recurrent condition, prevalent in the general population. In modern medicine, treatment modalities are aimed to diminish the incidence and extreme aggravation of clinical features. Nowadays, pippali rasayana being considered as a promising treatment approach for COPD. However, due to methodological limitations, there is no strong evidence to support pippali rasayana. Aim: The goal of the study is to evaluate the efficacy of Pippali Rasayana on pulmonary function in COPD patients Materials and Methods: It is double arm randomized placebo controlled single blind clinical trial. Total 60 patients of COPD will be randomly divided into two groups (each group contain 30). In both groups, standard treatment of modern medicine will be continued. With this, in Group A (Intervention), pippali rasayana 5 gm (25 gm twice a day after meal ) with honey will be given for 45 days and Group B (placebo group) will be given placebo (250 mg twice a day after meal ) with water for 45 days. Assessment will be done on 15 th , 30 th and 45 st day. Results: Result will be declared on the basis of effect of pippali rasayana with pulmonary function test as well as frequency of Dyspnea, Chronic cough, Excessive sputum production. Conclusion: This trial may provide evidence on the efficacy of pippali rasayanaon pulmonary function in COPD. Original Research Article Shinde and Kuchewar; JPRI, 33(61A): 171-176, 2021; Article no.JPRI.80044 172


BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is defined as preventable and curable lung infection with major additional pulmonary effect that may confer the rigorousness in particular patients. Chronic Obstructive Pulmonary Disease (COPD) is an inadequacy of airflow caused due to lessening of small bronchioles and damage of lung alveoli which is caused due to chronic inflammatory reaction in the lungs to the foreign particles. The most common respiratory features include cough, dyspnea and/ or intermittent production of sputum [12]. Chronic Obstructive Pulmonary Disease (COPD) is highest in patient who smoke or have history of tobacco use, those older than 40 years. It is observed that 70-80% exacerbation of COPD is elicited by bacterial or viral respiratory contagions. More than 3 million people died of COPD in 2012 accounting for 6% of all deaths worldwide. In coming decades due to constant contact to COPD risk factors and aging of the population COPD problem is probably increase [1,2].
In Ayurveda the features like cough, breathing difficulties are caused due to dushti(vitiation) of Pranavaha Srotas. Though it is difficult to correlate with any particular disorder of Pranvaha Sroto Dushti, but advanced condition of Doshika Kasa and Tamaka Shvasa may result into COPD [3,4,5]. In modern medicine, management procedure is targeted to diminish the incidence and severity of intensification of the clinical features. The classes of medications commonly used are Bronchodilators, Anti-inflammatory agents, Inhaled corticosteroids, Oral glucocorticoids etc. Other treatments are Pulmonary rehabilitation, Oxygen therapy, Ventilatory support, Lung volume reduction surgery, Bullectomy, Lung transplantation, Bronchoscopic interventions [6,7].

In
Samhitas,rasayanais described for rejuvenation.Naimittik Rasayana is specially mentioned for chronic illnesses. Naimittika rasayana is a type of Rasayana therapy advised for particular curative purpose. It quickens the recovery from prevalent illnesses. The main motive of Naimittika Rasayana is to treat particular illnesses in addition to restoring the health of individual [8]. In view of above facts this study is planned to assess the efficacy of the ayurvedic formulation Pippali rasayana is specially suggested in charaksamhita for disorders of Pranavaha strotas [9]. Pippali acts as vrishya ,rasayani, rechani and alleviator of kapha and vayu. It is mentioned in the treatment ofshwas ,kasa, udar, jwar, kushta, prameh, pleeha, arsha, shool and amavata. Pharmacological outlinedisplays that it acts as an anti-tubercular, antimicrobial, hepatoprotective, respiratory, neuroprotective, anti-diabetic and an aphrodisiac along with bioavailability enhancer [10].

METHODOLOGY
Type of trial -Double arm randomized placebo controlled single blind clinical trialAllocation ratio -Total 60 patients will be selected for the study which will be randomly divided into two groups. Both groups will continue their modern medicinal treatment suggested by pulmonologist. With this, group A (experimental group) will be given pippalirasayan and group B will be given placebo.

Drug Collection and Authentication:
The raw material will be procured from reliable source and will be authenticated from Department  [12].

Group B (Placebo Control):
Treatment of Modern medicine prescribed by pulmonologist + Placebo250 mg twice a day with water for 45 day's.

Criteria for Discontinuing or Modifying
Allocated Interventions: From the study if any untoward incidence, features of drug sensitivity or any other disease or problem arises, Subject will be withdrawn and free treatment will be offered to the subject till the difficulty subsides. We will measure quantity of Churna for the consumption of appropriate dose for assessment and to check drug adherence during treatment the subject will be followed up.
Follow up: Patients will be followed up on15 th day, 30 th day and 45 th day during the period of treatment.

Primary Outcomes:
The primary outcome is to check the effect of interventional drug on Pulmonary function test (PFT).

Secondary Outcomes:
The secondary outcome is to compare its effect on frequency of attacks of Cough and Dyspnea.
Statistical Analysis: Wilcoxon test. Paired as well as Unpaired t test will be used to analyse the data having objective criteria. The McNamara's test will be used to analyse the data with subjective criteria. Total follow up: Patient will be followed up thrice during the trial. First on 15 th day after initiating the treatment and then on 30 th day and on 45 th day.
Patient Recruitment: By computerized random chart sampling method 60 patient will be recruited (30 in each group).
Implementation: Principle investigator will enrol and allocate the patient.

Data Collection Method:
Subjective: Dyspnea, Chronic cough, Excessive sputum productionwill be assessed by gradation of symptoms.
Gradation with validation: Symptoms will be seen before, during and after treatment using gradation of symptoms for clinical research methodology. Attack lasting for duration of 1-6 hours. 3 Attack lasting for duration of 6-12 hours. 4 Attack lasting for duration of 12 hours. 5 Attack lasting for duration of more then 12 hours. Gait is gentle than individual of the similar age due to rapid breathing or has to take rest for breathing while walking at personal place on a flat surface. 3 Breathing is stopped while breathing out after walking of out 100 meter on a flat surface. 4 breathlessness while leaving the house or feel breathless while dressing or undressing. Continuously.
If the value of pulmonary function test is lies in between the FEV1 / FVC is 80% -120% or FEV1 / FVC will < 80% [10] then we concluded that Pippalirasayana is effective on patients of chronic obstructive pulmonary disease.

Plan to Promote Participant's Retention and Complete Follow Up:
We will stay in touch with the patient by taking contact number and timely advise them proper medication practices and follow up and the data regarding follow up will be stored in the documentation with valid reasons.
Data Management: The data will be collected from patients by assessor by doing clinical assessment after taking written consent form from the patient. Data will be entered in master sheet and analysed by using appropriate statistical technique and data coding will be done by principal investigator.

RESULTS
We hypothesised that in the group of pippali rasayana we may get improvement in pulmonary function test (PFT) than placebo group because 'Rasayana' are rejuvenators possesing strong antioxidant activity and antagonistic actions on the oxidative stressors [13]. Pippalihas a number of components, including volatile oil, alkaloids, isobutyl amides, ligansans ester. Piperine, which is a crucial component is having significant antiinflammatory action.
Pippali reduces inflammation of both acute and sub-acute phase [14]. Pippali has a property of antibacterial antifungal activity of various pathogenic bacteria and fungi respectively. Clinical studies have revealed that pippali is very effective in the treatment of bronchial asthma [15].

DISCUSSION
Study will observe that Pippali Rasayana along with treatment of Modern medicine will effectively reduce signs and symptoms of COPD.  [17].Therefore, collectively this drug helps in stroto shodhana and rejuvenate respiratory system which is the key factor in pathogenesis of COPD [18]. Related studies by Sourya et al. [19] and Patil et al. [20] were reviewed. Gupta et al. reported critical appraisal of pipasa in chronic obstructive pulmonary disease [21]. Studies on COPD from India were reviewed [22][23][24][25][26].

CONCLUSION
Conclusion will be drawn from outcome of the study.

NOTE
The study highlights the efficacy of "Ayurveda" which is an ancient tradition, used in some parts of India. This ancient concept should be carefully evaluated in the light of modern medical science and can be utilized partially if found suitable.

CONSENT
The written consent will be taken before starting the study from the patient. During the study the confidentiality of each patient will be properly maintained.