Clinical trial NCT01360788: GOLD Stage I Chronic Obstructive Pulmonary Disease (COPD)
Official title: GOLD Stage I COPD: Is it Really a Disease ? Exercise Tolerance, Muscle Function and Response to Bronchodilation in GOLD Stage I COPD Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mild Chronic Obstructive Pulmonary Disease
Respiratory Symptoms
Physical Activity
Keywords: chronic obstructive pulmonary disease
lung function
symptoms
activity-related dyspnea
quadriceps muscle function
exercise capacity
physical activity in daily life
muscle biopsy
systemic inflammation
GOLD stage I
pulmonary function
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: Pfizer
First posted: 2011-05-26
Enrollment: 53
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximal oxygen consumption
timeFrame: Baseline
Secondary outcomes:
measure: Quadriceps muscle force
timeFrame: Baseline
measure: Levels of physical activity in daily life
timeFrame: Baseline
measure: Oxydative stress
timeFrame: Baseline
measure: Pulmonary function
timeFrame: At baseline and before and 60-min after the nebulization of either placebo or bronchodilator
measure: Time to exhaustion during a constant intensity exercise test
timeFrame: Before and 90-min after bronchodilation or placebo
measure: Systemic inflammation
timeFrame: Baseline
measure: Quadriceps muscle endurance
timeFrame: Baseline
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
state: Quebec
Study officials:
affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
name: François Maltais, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.