Disease states that effect pulmonary function either impair ventilatory capacity or gas exchange (ventilation-perfusion mismatching) by impairing pulmonary circulation or both. Generally one is the predominant cause of pulmonary impairment.

Ventilation impairment is demonstrated by a low Breathing Reserve (the ventilatory capacity remaining at peak exercise that the patient could have utilized had the patient continued to exercise). In a normal subject it is 50% or higher at peak exercise; 30% is considered the lower limit of normal and 10% or is less is pathological and qualifies as a ventilation limitation.

Circulation impairment is demonstrated by a diminished ability to remove CO2 during exercise. The quantity of CO2 produced during exercise is reduced because the lungs are not being perfused by the right ventricle with CO2 rich blood or there are areas that are perfused but not ventilated and vice-versa. The differential for this is:

1. Thrombo-embolic disease
2. Pulmonary arterial hypertension
3. Pulmonary vascular disease (such as emphysema and interstitial fibrosis)
4. Moderate to severe left ventricular dysfunction

The diagnostic criteria for impaired pulmonary circulation are:

1. High ventilatory equivalents for O2 and CO2 (VE/VCO2 and VE/VO2) measured at the AT or the lowest value if the AT is not achieved. The ventilatory equivalents will decrease in a normal subject during exercise reaching a nadir (panel 6) and then increase after the AT. This pattern is blunted with impaired pulmonary circulation.

2. High end-tidal value for O2 (PetO2) and low end-tidal value for CO2 (PetCO2) are seen in panel 9. The PetO2 decreases with exercise and PetCO2 increases with exercise in the normal subject. This physiological effect is blunted with impaired pulmonary circulation due to limited gas exchange.

3. The VE to VCO2 slope (panel 4) will be increased.

4. Low peak respiratory exchange ratio (RER < 1.09)

5. Desaturation may occur at high workloads.

6. Patients are generally hungry for air (dyspnea) near peak exercise capacity when a pulmonary issue is limiting exercise. In contrast, patients with CV impairment tend to be fatigued near peak exercise.