Asymptomatic Versus Symptomatic Mild COPD: Comparisons at Rest and at Exercise
Asymptomatic Versus Symptomatic Mild COPD: Comparisons at Rest and at Exercise
The current definition of chronic obstructive pulmonary disease (COPD) is based on the
 presence of persistent airflow obstruction assessed by spirometry. About half of the subjects
 with mild COPD (i.e. reduced forced expiratory volume in one second (FEV1) on forced vital
 capacity (FVC) ratio along with normal FEV1] are asymptomatic. Subjects with symptomatic mild
 COPD have reduced exercise tolerance and abnormal dynamic ventilatory mechanics compared to
 healthy subjects. The physiological and perceptual responses to exercise of subjects with
 asymptomatic mild COPD are currently unknown.

 The purpose of this study is to assess exercise tolerance, ventilatory constraints on tidal
 volume expansion and dyspnoea in asymptomatic mild COPD subjects undergoing incremental cycle
 cardiopulmonary exercise testing (CPET) to the limit of tolerance compared with symptomatic
 mild COPD and healthy controls.
Subjects attend one single visit. If needed, COPD subjects are asked to stop any respiratory
 related medication such as short and long acting bronchodilators 72 hours prior to the visit.
 Subjects are asked to arrive early in the morning. After informed consent and appropriate
 screening of medical history, all subjects complete the mMRC scale. A complete medical
 history is collected. Subjects thereafter complete pulmonary function testing pre- and 30-min
 post-bronchodilator. Subjects are given a normal mixed meal and are asked not to drink
 alcohol or coffee.

 A symptom-limited incremental cycle exercise test is performed on the same day, at least 6
 hours after the bronchodilator test and at least 4 hours after the meal. After a steady-state
 resting period, a 3-min warm-up is conducted at about 20% of individually estimated maximal
 work load (Wmax), and the load is increased every minute in such a way that the test duration
 is >8 and <12 min. The following data are obtained breath by breath and expressed as 30-s
 averages: V'O2 and carbon dioxide production (V'CO2); minute ventilation (V'E); tidal volume
 (VT); respiratory rate; and ventilatory equivalents for oxygen and carbon dioxide. Blood
 pressure is measured every minute by a sphygmomanometer. Blood samples are withdrawn from the
 arterialized earlobe at rest and at near-maximal exercise. Tests are terminated at the point
 of symptom limitation (peak exercise). Upon exercise cessation, subjects are asked to
 verbalize their main reason for stopping exercise (breathing discomfort, leg discomfort or
 both).
Inclusion Criteria:

 -  For COPD groups: post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≥ 80%
 predicted and a FEV1/forced vital capacity (FVC) ratio < 0.70

 -  For the "Asymptomatic mild COPD" group: modified Medical Research Council (mMRC) score
 equal to zero and absence of respiratory symptoms including chronic cough and/or
 chronic expectoration and/or chronic wheeze.

 -  For the "Symptomatic mild COPD" group: mMRC) score > 0

 -  For the "Healthy controls" group: FEV1 > 80% predicted and FEV1/FVC > 0.7) and a mMRC
 score equal to zero and absence of respiratory symptoms including chronic cough and/or
 chronic expectoration and/or chronic wheeze

 -  Able to perform all study procedures and provide informed consent

 Exclusion Criteria:

 -  Presence of a medical condition other than COPD that could cause or contribute to
 breathlessness (i.e., a respiratory disease other than COPD and/or a metabolic and/or
 a cardiovascular disease)

 -  Presence of disorders other than COPD that could interfere with exercise testing, such
 as neuromuscular diseases or musculoskeletal problems

 -  History or clinical evidence of asthma

 -  Use of daytime oxygen or exercise-induced arterial oxygen desaturation to <80% on room
 air