Vitamin D3 supplementation dose not increase plasma antioxidant enzymes level in COPD patients was the null hypothesis of the research.

On the first day of enrollment, the objectives, nature, purpose and potential risk of all the procedures which are intended to be used for the study will be explained in detail to each COPD patients (diagnosed by pulmonologist), with a cordial attitude giving emphasis on the benefits he might obtain from this study. He will be encouraged for voluntary participation and will be allowed to withdraw himself from the study even after participation, whenever he feels uneasy. If he will agree to be enrolled in the study, an informed written consent will be taken in a prescribed form. Details family history, medical history and thorough physical examination of each patient will be done and all the information will be recorded in a standard data sheet. Then all the patients will be requested to attend the Department of Physiology at 8:30 am (after overnight fasting) on the examination day.

On that day, 16 ml of venous blood will be collected from antecubital vein of patient in different vacutainer tubes and will be taken to the laboratory of Department of Biochemistry and Molecular Biology as soon as possible, where 3 ml will be used for the estimation of serum vitamin D3 and rest will be preserved at -4˚C.

If the patient is with serum 25(OH)D <30 ng/ml (D3 deficiency) but >10 ng/ml (severe D3 deficient; for ethical purpose), then the serum parathormone (PTH), serum calcium, serum inorganic phosphate, serum alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), fasting blood glucose, serum glycosylated hemoglobin HbA1C, serum cholesterol, serum high density lipoprotein (HDL), serum low density lipoprotein (LDL), serum triglyceride (TG), serum creatinine will be assessed from the preserved blood. After getting all the biochemical reports the final selection will be done, according to the inclusion and exclusion criteria. In addition serum level of Catalase and Superoxide dismutase will be done in the Department of Physiology, BSMMU. Then all the eligible patients will be randomly assigned to either 'study (A)' or 'control (B)' group. These data will be recorded as values of 'day 0' (A0, B0).

Subsequently a standard therapeutic treatment (according to Global initiative for chronic obstructive pulmonary disease guideline) will be prescribed (by the pulmonologist) to all the selected stable COPD patients of both groups. Proper education will be given about drug, method of taking medication and medication plan.

Along with the standard pharmacological treatment of COPD, all patients of both the groups will be advised to have sunlight exposure (within 11 am to 2 pm) only for 20 minutes daily and also to continue ad lib (according to their own choice) diet. In addition, oral vitamin D3 (80,000 IU per week) and placebo will be added to the treatment schedule of the 'Study' patients and 'Control' patients, respectively, for consecutive 13 weeks.

Subsequently, all these patients (of both groups) will be cordially requested to attend the Department of Physiology on 13th week of their follow up, to reexamine the serum 25(OH)D and Calcium (to check the toxicity or deficiency). Then according to serum level of 25(OH)D and Ca, [vitamin D3 40,000 IU (1 capsule) per one to six weeks] (Vitamin D council 2019) will be again given to the 'Study' patients for further 13 weeks. On the other hand, if serum 25(OH)D is <10 ng/ml [severely deficient (vitamin D Council 2019)] of any 'control' patient, then he will be dropped out from the study (for ethical purpose) and a new COPD patient will be enrolled to fulfil the desired sample number. After that they will be cordially requested to visit again the Department of Physiology, BSMMU on '26th week' to reexamine all the study variables, and the data will be recorded as values of '26th week' (A2, B2).

During the entire study period (26 weeks), a good rapport will be kept by the researcher with every patient through taking time to time follow up over telephone and visiting patient's place with scheduled appointment to maintain a proper follow up at 2nd (at 13th week) and 3rd (at 26th week) visit of the study.

Any patient, who will fail to follow the study procedure exactly during study period, he will be dropped and a new one will be included to fulfil the desired total sample.

Inclusion Criteria:

• Pulmonologist diagnosed COPD patients

Duration of COPD: 1-10 years

Vitamin D3 deficient : Serum 25(OH)D <30 ng/ml

Age: >40years

Sex: Male

Socioeconomic status: Middle class

smoker

Exclusion Criteria:

• With acute exacerbation of:

any other pulmonary diseases like - bronchial asthma respiratory tract infection bronchiectasis pneumothorax pleural effusion tuberculosis pulmonary fibrosis pneumonectomy or pulmonary lobectomy any cardiac disease, like -

• unstable angina pectoris
• congestive heart failure
• myocardial infarction
• cardiac arrhythmia