GOLD Stage I Chronic Obstructive Pulmonary Disease (COPD)
Condition: Mild Chronic Obstructive Pulmonary Disease; Respiratory Symptoms; Physical Activity
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Signs and Symptoms, Respiratory
Study type: Observational

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.
    

Intervention name(s): Combination ipratropium/salbutamol or placebo (nebulization)
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Combivent or placebo (nebulization)
Intervention MeSH terms: Albuterol; Ipratropium
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.
      
Biospecimen description: 
      Muscle biopsies Venous blood samples
    
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