Evaluating the clinical efficacy of Musta-Sunthi Kwath as an add-on to Ayurvedic Inhalation Therapy followed by Rasayana therapy in the Management of Smoking-induced Chronic Obstructive Pulmonary Disease (Tamaka Shwasa)A Randomized Comparative Clinical Trial

Research Question

Does the addition of Musta-Sunthi Kwath to Ayurvedic inhalation therapy (aerosol) improve the clinical outcomes in patients with smoking-induced Chronic Obstructive Pulmonary Disease (Tamaka Shwasa) compared to inhalation therapy Followed by Rasayana Therapy?

HYPOTHESIS:

The addition of Musta-Sunthi Kwath to Ayurvedic inhalation therapy followed by Rasayana Therapy significantly improves clinical outcomes in patients with smoking-induced Chronic Obstructive Pulmonary Disease (Tamaka Shwasa).

Null Hypothesis (H0)

There is no significant difference in clinical outcomes between the group receiving Musta-Sunthi Kwath with Ayurvedic inhalation therapy and the group receiving Ayurvedic inhalation therapy(aerosol) followed by Rasayana Therapy in the management of smoking-induced COPD (Tamaka Shwasa).

Alternative Hypothesis (H1)

There is a significant improvement in clinical outcomes in the group receiving Musta-Sunthi Kwath with Ayurvedic inhalation therapy(aerosol) compared to the group receiving Ayurvedic inhalation therapy followed by Rasayana therapy in the management of smoking-induced COPD (Tamaka Shwasa).

Chronic Obstructive Pulmonary Disease COPD is a progressive and irreversible respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. According to the World Health Organization it is the fourth leading cause of death worldwide affecting more than 300 million people. In India COPD accounts for nearly 10 percent of adult respiratory cases with a higher prevalence among men due to elevated tobacco use.

Tamak Shwasa is generally correlated with Bronchial Asthma and no absolute correlation is given for COPD. However it is important to note that the differential diagnosis of Asthma and COPD is based on the reversibility or irreversibility of the airways. Therefore we can say that Tamak Shwasa after one year of chronicity can be correlated with COPD because of the irreversible nature that explains its incurability. According to Acharya Charaka Tamak Shwasa becomes Yapya manageable but not completely curable after one year which can be correlated with Chronic Obstructive Pulmonary Disease COPD.

Inclusion Criteria

1.Participants aged between 21 and 65 years, irrespective of gender, will be included in the study

2.Having sign and symptoms of Tamakshwasa– swasakruchhrata (dyspnea), kanthodhwansa (speak with difficulty), kasa (cough), ghurghurka sabda (wheezing/rhonchi)

3.Newly Diagnosed COPD (GOLD stage I & II): post-bronchodilator FEV1/FVC ratio less than 0.7); FEV1 greater than or equal to 50 and lesser than 80% of predicted normal; MRC dyspnoea scores greater than or equal to 2.

4.History of smoking of at least 10 pack-years.

5.Patients Having Smoking Index (greater than or equal to 200)

6.Elevated Exhaled CO levels (greater than or equal to 2ppm) measured by Smokerlyzer

7.Patients willing to provide informed written consent and comply with study procedures.

8.Not undergoing any other lung rehabilitation therapy

Exclusion Criteria

1.COPD with life threatening complications like cor-pulmonale, respiratory failure, pneumothorax and polycythemia

2.Patient taking steroid therapy  (systemic or inhaled corticosteroid)

3.Known Case of asthma.

4.History of cystic fibrosis.

5.Past or current malignancy within 5years.

6.Pregnant women and lactating mothers.

7.History of any adverse drug reactions.

8.Patients having positive HIV1 and 2 or positive Hepatitis B.

9.Patients having  end stage hepatic dysfunction (defined aspartate aminotransferase  (AST) and/or alanine aminotransferase (ALT) greater than 4 times of the upper normal limit) or severe renal dysfunction (defined as  S. creatinine more than 1.2 mgdl),severely compromised cardiac function (EF less than 30% ).

10.Patient with poorly controlled Hypertension ( greater than 160/100 mm Hg)

Investigations required for Allocation

PFT      Smokerlyzer(co level)      FeNO      Chest X-ray (PA View)      CBC With ESR      Sputum For AFB for 3 consecutive days      TB GOLD

  Investigations During Follow-up

All patient will be daily monitor in IPD for 15days and then after 15days during rasayan therapy

PFT ,Smokerlyzer,FeNO and symptoms assessment will be done on every visit.

All the patients will be planned to undergo following laboratory investigations before  and after the treatment-

CBC With ESR , CHEST X-ray PA view

Exercise tolerance (6 MWT)

COPD assessment test score ,Modified Medical Research Council (mMRC) questionnaire , St. George Respiratory disease questionnaire, SF-36 questionnaire (COPD specific)

Primary Outcome Measures

1. Improvement (10-20%) in below test parameters

Forced Expiratory Volume in 1 second (FEV1)

FEV1 by FVC ratio by spirometry

Secondary Outcome Measures

1. Reduction in exhaled carbon monoxide levels (10-20%) via Smokerlyzer indicating smoking cessation or reduction
2. Reduction in exhaled fractional nitric oxide (20-25%) by FeNO
3. Change in clinical scores and questionnaires:

COPD Assessment Test (CAT)

Modified Medical Research Council (mMRC) Questioner

St. George’s Respiratory Questionnaire (SGRQ)

SF-36 questionnaire (COPD-specific)

4. Change in laboratory parameters

CBC With ESR

5. Exercise tolerance and functional capacity

6-Minute Walk Distance (6MWD)

Oxygen saturation during exercise

Dyspnoea level (BODE Index)

Time frame: Evaluations conducted over 15 to 75 days, with follow-ups at Day 15, 30, 45, and 60 and 75th day

METHODOLOGY:

1)

Study design

Randomized Controlled Trial

|Study type

Comparative

  |Timing

Prospective

  |Masking

Open Label

  |Sample size

30 in each group

|Selection of cases

O.P.D. /I.P.D. wing of Department of Kayachikitsa, All India Institute of Ayurveda on the basis of screening proforma

|No. Of groups

2

|Sampling method

Computer generated Randomization sequence (GraphPad QuickCalcs)

|Duration of trial

75 days

|Duration of intervention

45 days

|Follow Up

During treatment: 1st day and15th day daily IPD 30th day 45TH day

After treatment 60th 75th day

 (2) Duration of Trial:

Washout period 2week(14days)

Total duration of trial (clinical trial duration plus Follow up duration)- 75days

Duration for Nebulization therapy 15 days

Duration of Musta Sunthi Kwath    15days

Duration of Rasayan Therapy         30days

(3) Follow up studies: -

The entire patient of two groups will be regularly follow-up once after 15 days clinical trial and then on 75th day of trial

SAMPLE SIZE CALCULATIONStudy aims to evaluate the add on effect of Musta Sunthi kwath on Smoking induced COPD. The statistically significant sample size is determined following the existing available data records generated in the laboratory of authors.  The outcome measures of previous randomized clinical trials using aerosol could reveal significant improvement in drug intervention group among the patients with age group (18years to 60years). It is expected that the proposed study would also generate the identical outcome with power 80% and confidence level of 95% (ALPHA 5 %) and mean difference of 0.6 and standard deviation of 1. This has generated a requirement of 44 subjects in each arm of the proposed clinical trial. Assuming 10% withdrawal from each group, it is required to constitute each group with 48 subjects.

SAMPLE SIZE

According formula total no. of 48 sample required in each group. but due to time and budget constraint total number of 30 cases will be included in each group in the proposed clinical trial. Days after completion of trial.

All the patients will be planned to undergo following laboratory investigations before and after the treatment.