Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient

change of frequency-tidal volume pattern

the inspiratory time (Ti, measured in second) , the expiratory time (Te,measured in second) and the respiratory frequency

Time frame: Baseline, at 1 month

Tidal volume Largest Lyapunov component (an indicator of the sensitivity of the system to initial conditions)

Time frame: Baseline, at 1 month

change of resistance at 5Hz , at 20 Hz

The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Resistance is complex measure that incorporates the lack of changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device. AX and resonant frequency are correlated to reactance.

Time frame: Baseline, at 1 month

Change of reactance

the fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency at 5Hz was used. Reactance is thought to reflect the elastic properties of the lung. All these measurements are expressed in the same unit (for resistance and reactance) and refer to oscillatory mechanics obtained by the same device.

Time frame: Baseline, at 1 month

Change of AX and resonant frequency

Area under reactance curve (AX) and resonant frequency are correlated to reactance.

Time frame: Baseline, at 1 month

change of spirometry parameters

Spirometry : FEV1, FVC, FEV1/FVC

Time frame: at 1 month

change in lung function as assessed through body plethysmography

Change from baseline to end of treatment in the following measures Total lung capacity (TLC) Residual volume (RV) Inspiratory capacity (IC) Functional residual capacity (FRC) All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated. For instance IC is TLC- FRC.There is no reason to separate these outcome measures

Time frame: Baseline, at 1 month

change of airway resistance (RAW) and specific airway conductance (sGAW).

sGaw is specific conductance, ie 1/resistance divided by the volume at which resistance was measured. These two parameters are always measured and used together. All plethysmographic parameters shown here are lung volumes, expressed in liters, and are somewhat interrelated.

Time frame: Baseline, at 1 month

Visual Analogic Scale

Two VAS (± 100 mm ) will be used to evaluate changes (much worse-unchanged-much better) in dyspnea and chest tightness 2 hours after PT003 administration and at 4 weeks in through and post dose conditions

Time frame: Baseline, at 1 month

Likert scales

Likert scales (7 points) will assess changes in dyspnea and global health at visit 3 in comparison with pre treatment condition (V2).

Time frame: Baseline, at 1 month

BDI/TDI

The BDI/TDI is an instrument developed to provide a multidimensional measure of dyspnea in relation to activities of daily living. The Baseline Dyspnea Index (BDI) provides a measure of dyspnea at a single state, the baseline, and the Transitional Dyspnea Index (TDI) evaluates changes in dyspnea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference (MC

Time frame: Baseline, at 1 month

mMRC dyspnea scale

The Modified Medical Research Council (mMRC) dyspnea scale uses a simple grading system to assess a subject's level of dyspnea that consists of five statements about perceived breathlessness. It is an interviewer-administered ordinal scale on which subjects provide their dyspnea according to five grades of increasing severity (scores ranges from 0 (none) to 4 (very severe).

Time frame: Baseline, at 1 month

Modified Dyspnea Profile (MDP)

The MDP consists of 11 items evaluating both the sensory and affective dimensions of dyspnoea. One item (A1) assesses the unpleasantness of dyspnoea on a 0-10 visual numerical scale anchored by "neutral" (0) and "unbearable" (10). Five items assess the sensory dimension of dyspnoea, both in terms of quality and intensity (on a scale of 0-10). Five items assess the affective dimension of dyspnoea, also in terms of quality and intensity (on a scale of 0-10).

Time frame: Baseline, at 1 month