Chronic obstructive pulmonary
disease also known as COPD is one of the three most common causes of death. Its chronic nature and association with
comorbidities lead to an increased economic burden on countries. This problem
is expected to increase in future due to rising smoking trends even in females
additionally due to the ageing of the population in most countries of the
world. The renin angiotensin aldosterone system, also known as RAAS, is a vital system
of the human body, which maintains plasma sodium concentration, arterial blood
pressure and extracellular volume.
The RAAS is a hormonal system for which the primary effector is angiotensin 2, derived
from stepwise proteolytic cleavage of angiotensinogen. Angiotensin 2 then, is a
stimulator of aldosterone synthesis. Therefore, angiotensin 2 and aldosterone
are the primary endpoints of the hormonal system. Angiotensin
II is a versatile effector peptide hormone. Every organ is affected by RAAS
activation resulting in hypertension, cell proliferation, inflammation, and
fibrosis. Imbalance of renin and angiotensin II can result in an overwhelming
number of chronic and acute diseases. RAAS is influenced by other enzymes,
hormones, pumps and signalling pathways. Thus RAAS can cause systemic inflammation
and vice versa.
Raas is well studied in hypertension but not
well-studied in the context of COPD. In this study, we will compare whether any
difference in the baseline inflammatory markers and RAAS in the control, COPD
and COPD with hypertension group. Additionally, if these groups (except
controls) treated with ACE inhibitor and ARB lead to improvement in the level
of inflammatory markers, RAAS and lung function
RESEARCH GAP 1. The association between
RAAS and Hypertension has been studied well as compared to the association
between RAAS and COPD.
2.
Studies related to these have been conducted more in the Western population.
3.
Very few studies, related to this in India have been done mainly in the South
Indian population.
4.
None of the studies, related to the effect of ACE inhibitors
and ARB on respiratory inflammation and lung function have been conducted.
OBJECTIVES 1.
To study various inflammatory
markers like Interleukin 2, Interleukin 4, Interleukin 6, INF alpha, TNF gamma, hS CRP, renin, angiotensin,
aldosterone, ACE 2, and lung function among COPD and COPD with Hypertension
patients as compared to control.
2. To evaluate the effect of ACE Inhibitors
and ARB on various inflammatory markers like Interleukin 2, Interleukin 4, Interleukin 6, INF alpha, TNF gamma,
hS CRP, renin, angiotensin, aldosterone and ACE 2 in COPD and COPD with
hypertension group.
3.
To evaluate the effect of ACE Inhibitors and ARB on lung functions in COPD and
COPD with hypertension group.
This
clinical trial will be conducted on healthy volunteer, patients of COPD and
COPD with hypertension at the Department of Respiratory Medicine and Department
of Medicine, School of Medical Sciences and Research and Sharda Hospital for 12
months
there
will be a total of 80 individuals in each limb
INCLUSION
CRITERIA FOR EACH GROUP A. CONTROLSThe control healthy individuals will comprise volunteers with
no apparent history and signs of any cardio-pulmonary disease. Both male and
female volunteers with age more than years and of the same ethnicity will be
recruited for the study. They will be recruited in the study after fulfilling inclusion and exclusion criteria. Medical history will be taken
with prior written informed consent from all the volunteers. Volunteers with
any cardio-pulmonary ailment will be excluded from the study.
B. COPD Patients reporting to Sharda
Hospital with COPD of all 3 groups that is, A, B and E according to GOLD guideline
2024 will be recruited for the study after various clinical investigations.
Previously diagnosed patients and newly diagnosed patients treated with
standard protocol for COPD, for at least 2 months will be recruited.
C. COPD WITH
HYPERTENSION Patients of COPD as per criteria mentioned in para B with
newly diagnosed or previously diagnosed patients of hypertension, not treated
with ACE II inhibitors and ARBs, reporting to Sharda Hospital with any grade
of hypertension according to the American College of Cardiology/American Heart
Association will be recruited for the study.
EXCLUSION CRITERIA Patients with bronchial asthma, active tuberculosis, signs and symptoms of
clinically significant neurological, psychiatric, renal, immunological,
gastrointestinal and urinogenital disorders; endocrine disorders (uncontrolled
diabetes or thyroid disease) or uncontrolled haematological disease, unstable
liver disease and unstable or life-threatening heart disease, cancer patients
and patients with any drug, substance or alcohol abuse will be excluded
SCREENING PARAMETERS Blood sugar (random), CBC, LFT, KFT, ECG and X ray chest (PA view) will be done
to fulfil the inclusion criteria
STUDY PARAMETERS Pre-application of the drug, Renin, Angiotensin, Aldosterone,
ACE 2, Interleukin 2, Interleukin 4, Interleukin 6, INF alpha, TNF gamma, hS CRP and lung function
will be performed and comparison will be made between various values in
controls, COPD and COPD with hypertension.
RANDOMIZATION In this
trial, randomization will not be done as most of the COPD patients with
advanced disease were diagnosed several years ago and on standard treatment
since then, hence any effects of drugs used as standard care for COPD would
occur by that time
Patients of groups B and
C, that is COPD and COPD with hypertension will be treated with capsule Ramipril
5.0 mg, an angiotensin converting enzyme and tablet Telmisartan 40 mg, an
angiotensin receptor blocker for 90 days
Then, all the parameters
that is, Renin, Angiotensin, Aldosterone, ACE 2 Interleukin 2, Interleukin 4, Interleukin 6, INF alpha, TNF gamma
EXPECTED OUTCOMESThis
study on its successful completion will provide new insight into the treatment
of COPD and COPD with hypertension.
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