Effects of a Physical Exercise Program on the Responses Measured by HIF-1 Related to Ventilatory and Hematological Function in Patients With COPD Resident at 2600 m.s.n.m.
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Nuclear concentration of HIF-1
Study Overview
Brief Summary
Despite being considered a potentially preventable disease, COPD is classified as one of the respiratory problems with the highest prevalence and socioeconomic impact. According to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD), people with COPD require actions that optimize quality of life by improving lung function and increasing tolerance to fatigue.
Research such as those carried out by Semenza, establish that metazoan organisms such as the human species present biomolecular mechanisms for O2 homeostasis, based on transcriptional changes that allow regulating or modifying the responses necessary for the maintenance of the cellular metabolic functions. Hypoxia Induced Factor 1 (HIF-1) is the primary molecular mechanism for the regulation of O2-regulated genes in nuclear cells; Therefore, they promote adaptive mechanisms to hypoxia, through the generation of protein synthesis that favor processes such as erythropoiesis, angiogenesis, changes in oxidative metabolism and modification of the pulmonary vascular response.
Research carried out in cells of people with COPD exposed to environmental hypoxia by low oxygen pressure (PO2), have shown changes in the nuclear concentrations of HIF-1, affecting the transcriptional mechanisms of specific genes for Erythropoietin (EPO), the Factor of Vascular Endothelial Growth (VEFG) and therefore limit the generation of essential proteins for systemic responses. These transcriptional mechanisms are conditioned by the structural changes of chromatin seconded by the inhibition in the performance of histone enzymes, which influences the synthesis of proteins involved in metabolic, hematological and / or ventilatory processes as a response. to hypoxia. However, the concentration and effect of HIF 1 on the synthesis of EPO and VEGF and its relationship with spirometric and hematological tests have not been studied in COPD people who live in medium altitudes and who are additionally exposed to additional hypoxic stimuli such as exercise physical.
Although it is known that in COPD there is a decrease in the diffusion of O2 through the blood-gas barrier generating hypoxia and that with low PO2 there are biomolecular adaptations to favor oxygenation, perfusion, and metabolism; At the moment, the responses of HIF-1 and its effect on the generation of proteins associated with erythropoiesis and angiogenesis (EPO, FEVG) in people with COPD with physical exercise-based treatments are unknown.
Detailed Description
- General objective
To determine the effect of a physical exercise program on the responses mediated by HIF-1 in COPD patients resident at 2600 m.s.n.n. 2. Research question.
What is the effect of a physical exercise program on the responses mediated by HIF-1 in COPD patients resident at 2600 m.s.n.n? 3. Type of study.
It is presented as a quasi-experimental study with intra- and inter-group comparison before and after, with an external control group. Two observations will be made in time (pre and post test); Comparisons will be made intra-group and between groups, as follows:
Experimental group 1:
- G1: People with a diagnosis of COPD stratified in GOLD 1-2.
- O1: Measurement of HIF-1, HADC 7, EPO Synthesis, VGEF Synthesis, FEV1, Hemogram.
- X: Application of the physical exercise program.
- O2: Measurement HIF-1, HADC 7, EPO Synthesis, VGEF Synthesis, FEV1, Hemogram.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Masking Description
Unique masking when study participants, who will not know:
- Assignment to research groups, for which the measurement of the severity of the disease will be developed individually.
- Treatment to receive, for which the intervention will be carried out individually and at the home of each participant.
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
- •People with a diagnosis of COPD categorized in GOLD 1,2,3 and 4, with no record of respiratory crises in the last 3 months.
- •People with a diagnosis of COPD categorized by lung function in GOLD 1,2,3 and 4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
- •People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
- •People who have read and signed informed consent and who have membership in a mandatory health plan.
Exclusion Criteria
- •People with a medical diagnosis of anemia, liver disease, chronic kidney disease, rheumatological diseases or a history of gastrointestinal bleeding in the last 2 months.
- •People with a diagnosis of COPD who have a history of kidney or liver transplantation.
- •People with a diagnosis of COPD who present severity of symptoms and/or respiratory exacerbations categorized in D presenting an mMRC > 2 and CAT > 10 with >1 hospitalization requirements.
- •People who are under pharmacological management with erythropoietin (EPO), antibiotics and / or steroids on a chronic basis.
- •People with musculoskeletal injuries that limit the execution of the physical training program or that present medical restrictions for the execution of physical exercise.
- •People with a diagnosis of COPD who record active smoking.
- •People who are participating in research related to medical, pharmacological or physiotherapeutic intervention protocols.
Arms & Interventions
G1: People with a diagnosis of COPD stratified in GOLD 1-2.
- Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
- People with a diagnosis of COPD categorized in GOLD 1-2, with no record of respiratory crises in the last 3 months.
- People with a diagnosis of COPD categorized by lung function in GOLD 1,2,3 and 4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
- People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
- People who have read and signed informed consent and who have membership in a mandatory health plan.
Intervention: Physical exercise program (Other)
G1: People with a diagnosis of COPD stratified in GOLD 1-2.
- Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
- People with a diagnosis of COPD categorized in GOLD 1-2, with no record of respiratory crises in the last 3 months.
- People with a diagnosis of COPD categorized by lung function in GOLD 1,2,3 and 4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
- People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
- People who have read and signed informed consent and who have membership in a mandatory health plan.
Intervention: Health education in COPD (Other)
G2: People with a diagnosis of COPD stratified in GOLD 3-4.
- Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
- People with a diagnosis of COPD categorized in GOLD 1,2,3 and 4, with no record of respiratory crises in the last 3 months.
- People with a diagnosis of COPD categorized by lung function in GOLD 3-4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
- People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
- People who have read and signed informed consent and who have membership in a mandatory health plan.
Intervention: Physical exercise program (Other)
G2: People with a diagnosis of COPD stratified in GOLD 3-4.
- Adult person, over 40 years of age, both sexes, resident in medium altitudes or 2,600 meters above sea level in the last 2 years.
- People with a diagnosis of COPD categorized in GOLD 1,2,3 and 4, with no record of respiratory crises in the last 3 months.
- People with a diagnosis of COPD categorized by lung function in GOLD 3-4 and by severity of symptoms in A, B and C, without the need for supplemental oxygen.
- People with a diagnosis of COPD settled and domiciled for a minimum time of 14 months at moderate altitudes or 2600 m.a.s.l.
- People who have read and signed informed consent and who have membership in a mandatory health plan.
Intervention: Health education in COPD (Other)
G3: Control - People without a COPD diagnosis.
Healthy people, over 40 years old. No history of cigarette smoking or exposure to wood smoke. Who do not present diagnoses of musculoskeletal injuries and who are residents at 2600 meters above sea level for more than 14 months. With affiliation to a mandatory health plan and signature of informed consent.
Intervention: Physical exercise program (Other)
Outcomes
Primary Outcomes
Nuclear concentration of HIF-1
Time Frame: 1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.
Changes in the nuclear concentration of hypoxia-inducible factor (HIF-1) in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.
Synthesis of EPO protein.
Time Frame: 1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.
Changes in the synthesis of Erythropoietin (EPO) protein synthesis in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.
VEGF protein synthesis.
Time Frame: 1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.
Changes in the synthesis of the Vascular Endoletial Growth Factor (VEGF) protein in plasma. For this, an enzyme-linked immunosorbent assay (ELISA) will be executed using specific antibodies to immobilize the study proteins on a plate for their subsequent detection, with chemiluminescence detection.
Secondary Outcomes
- Chair Stand Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Arm Curl Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Blood hemoglobin (Hb)(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- 6 Minute WalK Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Forced expired volume in the first second (FEV1)(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Medium corpuscular volume (MCV)(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Chair-Sit and Reach Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Functional Vital Capacity (FVC)(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- FEV1/FVC ratio(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Erythrocyte count(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Back Scratch Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- 8-Foot up and go Test(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)
- Mean Corpuscular Hemoglobin (HCM)(1. Initial measurement (week 0) before the application of the physical exercise program. 2. Final measurement (week 8) after completion of the intervention program.)