GOLD Stage I Chronic Obstructive Pulmonary Disease (COPD) (GOLD)

GOLD Stage I COPD: Is it Really a Disease ? Exercise Tolerance, Muscle Function and Response to Bronchodilation in GOLD Stage I COPD Patients

Recently integrated in clinical practice, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification states that a mild (stage I) chronic obstructive pulmonary disease (COPD) is present, in a smoker, when the postbronchodilator forced expired volume in 1 second (FEV1) to forced vital capacity (FVC) ratio is < 0.7. A major change that was introduced by the GOLD classification system was that COPD could be diagnosed despite an FEV1 that is within normal predicted values (above 80% predicted). Because it suggests diagnosing and detecting COPD earlier than done until very recently in medical practice, the GOLD standards bring in a new reality to clinicians. In fact, this novel COPD classification comes with new research challenges because the functional impacts and systemic consequences related to COPD are mostly documented in patients with moderate to severe stages with little information specifically in GOLD stage I COPD. This information is important if the investigators are to convince physicians that GOLD stage I COPD needs to be diagnosed and eventually treated.

The investigators aimed to characterize GOLD stage I COPD patients according to activity-related dyspnea. More specifically, our objectives were to compare:

i) baseline pulmonary function ii) exercise capacity iii) quadriceps muscle function iv) levels of physical activity in daily life

between symptomatic (Sx) GOLD stage I COPD patients, asymptomatic (ASx) GOLD stage I COPD patients and healthy control subjects (CTRL). The investigators reasoned that exercise tolerance and physical activity levels would be decreased in Sx GOLD stage I COPD patients as it would be similar between ASx GOLD stage I COPD patients and CTRL.

Study Overview

• Status: Completed
• Conditions: Physical Activity; Respiratory Symptoms; Mild Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Combination ipratropium/salbutamol or placebo (nebulization)

Detailed Description

The study will be conducted among three subgroups: symptomatic GOLD stage I patients with COPD, asymptomatic patients GOLD stage I COPD and healthy control subjects with normal lung function. Subjects will be paired for age, sex and smoking history. The project will require three visits. In the initial visit, assessment of the pulmonary function with respiratory symptoms quantification will allow to classify subjects in the proper subgroup. The Medical Research Council (MRC) dyspnea scale will serve as the reference outcome to determine whether COPD patients are symptomatic or not. Patients with an MRC dyspnea score < 2 will be considered asymptomatic. A second questionnaire (ATS-DLD-78) will serve to document cough, expectorations, wheezing and smoking history in every subjects. Body composition will be measured by bioimpedance and by waist circumference after a blood sample taken in the morning, in a fasting state. A six-minute walk test (6MWT) will be performed by all subjects. After a one-hour resting period, a maximal incremental shuttle walking test will be realized in the same visit to quantify maximal exercise capacity. Measures of force and endurance of the quadriceps will be taken by magnetic stimulation of the femoral nerve before the maximal walking test. Finally, subjects will receive a portable device to monitor physical activity for a period of 7 days.

In the 2nd and 3rd visits, subjects will realize an endurance walking test at 85 % of their predetermined maximal capacity. Before each endurance test, a bronchodilator or a placebo will be administered following a randomized double-blind design. Measures of force and endurance of the quadriceps will be taken by magnetic stimulation of the femoral nerve before and 10-min after endurance exercise tests. A needle biopsy of the vastus lateralis will be performed at the end of the third visit.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Institut universitaire de cardiologie et de pneumologie de Quebec - Universite Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants were recruted after a participation to a research protocol on i) prevalence of COPD in Canada and ii) early detection of lung cancer. Finally, some participants were recruited following medical consultation with a pneumologist.

Description

Inclusion Criteria:

• Smoking history (≥ 10 pack/year)

Exclusion Criteria:

• Anticoagulation or coagulation defect
• Hypoxemia or exercise-induced desaturation (SpO2 < 85%)
• Antibiotic or oral corticosteroid therapy (end of treatment < 1 month prior to study)
• Anti-inflammatory treatment, exacerbation (< 3 months)
• Myopathy
• Neuromuscular or locomotor diseases
• Recent cancer
• Unstable cardiac condition
• Asthma

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy control subjects; Subjects with a significant smoking history (more than 10 pack-years) and a normal lung function.
Asymptomatic GOLD stage I COPD patients; GOLD stage I COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] > 80% predicted and FEV1/ forced vital capacity [FVC] < 0.7 and a smoking history > 10 pack-years) were recruited. A Medical Research Council (MRC) dyspnea score ≥ 2 was used to define the presence of symptoms (dyspnea). Concretely, this group did not present any respiratory symptoms, with a MRC dyspnea score of 1/5.	Drug: Combination ipratropium/salbutamol or placebo (nebulization); The COPD patients were randomly assigned a combination of ipratropium/salbutamol or a placebo in a double-blind crossover design. The bronchodilation produced by the medication was given in order to evaluate if bronchodilation was effective in increasing exercise tolerance during an endurance shuttle walking test in patients with GOLD stage I COPD.; Other Names: Combivent or placebo (nebulization)
Symptomatic GOLD stage I COPD patients; GOLD stage I COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] > 80% predicted and FEV1/ forced vital capacity [FVC] < 0.7 and a smoking history > 10 pack-years) were recruited. A Medical Research Council (MRC) dyspnea score ≥ 2 was used to define the presence of symptoms (dyspnea) in this group.	Drug: Combination ipratropium/salbutamol or placebo (nebulization); The COPD patients were randomly assigned a combination of ipratropium/salbutamol or a placebo in a double-blind crossover design. The bronchodilation produced by the medication was given in order to evaluate if bronchodilation was effective in increasing exercise tolerance during an endurance shuttle walking test in patients with GOLD stage I COPD.; Other Names: Combivent or placebo (nebulization)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal oxygen consumption	Exercise capacity was directly assessed following an incremental progressive shuttle test. The exercise capacity was defined as the maximal oxygen consumption (VO2 peak, ml/kg/min) by direct measurements of gas exchanges.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quadriceps muscle force	Quadriceps muscle strength was measured with magnetic stimulation of the femoral nerve. Mid-thigh cross-sectional area (MTCSA) was obtained following a computed-tomography scan. Quadriceps muscle biopsy was performed to measure muscle metabolism.	Baseline
Levels of physical activity in daily life	A portable armband was worn by the participants on a 7-days basis to monitor physical activities in daily life.	Baseline
Oxydative stress	Oxydative stress will be quantified in the blood and in the muscle samples obtained during the muscular biopsy.	Baseline
Pulmonary function	Pulmonary function will be measured by spirometry and plethysmography in the initial visit. In the subsequent visits, pulmonary function will be measured by spirometry before and 60-min after the nebulization of either placebo or bronchodilator. A computed-tomography scan of the lungs was also assessed	At baseline and before and 60-min after the nebulization of either placebo or bronchodilator
Time to exhaustion during a constant intensity exercise test	Time to exhaustion was also defined as exercise tolerance and was assessed during a endurance shuttle walking test 90-min following the nebulization of whether Combivent or Placebo in a double-blind crossover design. It was defined as the time in seconds for which a subject could maintain an intensity of 85% of the maximal oxygen consumption during walking or running.	Before and 90-min after bronchodilation or placebo
Systemic inflammation	Systemic inflammation will be studied from blood samples obtained in every participants.	Baseline
Quadriceps muscle endurance	Quadriceps muscle endurance was defined as the time to exhaustion following a constant quadriceps force corresponding to 50 % of the maximal voluntary contraction.	Baseline

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: Pfizer; Boehringer Ingelheim
• Investigators: Principal Investigator: François Maltais, MD, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Publications and helpful links

General Publications

• Gagnon P, Casaburi R, Saey D, Porszasz J, Provencher S, Milot J, Bourbeau J, O'Donnell DE, Maltais F. Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease. PLoS One. 2015 Apr 23;10(4):e0123626. doi: 10.1371/journal.pone.0123626. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: May 12, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Estimate): May 26, 2011
• Last Update Submitted That Met QC Criteria: May 24, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: lung function; exercise capacity; pulmonary function; symptoms; chronic obstructive pulmonary disease; systemic inflammation; muscle biopsy; activity-related dyspnea; quadriceps muscle function; physical activity in daily life; GOLD stage I
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Signs and Symptoms, Respiratory; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Ipratropium
• Other Study ID Numbers: GOLD-20378