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.

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.

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

Spirometry : FEV1, FVC, FEV1/FVC

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

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.

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

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

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

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).

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).