Recognition of Early Pulmonary Structural Changes by Using Real-time High Fidelity Expiratory CO2 Analysis

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is responsible for over 6% of all-cause mortality. Due to aging societies and exposure to risk factors, increasing prevalence is expected in the following years. Cigarette smoking is the most important risk factor for COPD, but also non-smokers may develop the disease. Although COPD is primarily seen as obstructive airway disease, it may also affect the lung parenchyma, the lung vessels, the systemic vessels, the heart and other organs. Therefore, COPD may be seen as a "pulmonary component of a systemic disease ". According to recent evidence patients with COPD and relevant lung vessel disease are at a higher risk to develop exacerbations and have worse prognosis. Usually, COPD patients suffer from a mild pulmonary hypertension, however some of them may present with a "pulmonal vascular phenotype" (PVP). Patients with PVP usually suffer from a relatively mild airway obstruction and are characterized by pathological changes in the small lung vessels, strongly elevated pulmonary vascular resistance, severely reduced diffusion capacity, normo- or hypocapnia, circulatory limitation of exercise capacity and a progressive right heart failure. Early recognition and therapy of COPD may stop further progression of the disease and the development of complications including changes in the small lung vessel.

Interstitial lung diseases (ILD) are characterized by structural changes in the lungs with fibrotic destruction and loss of alveolar tissue. Male gender and smoke exposure are frequent risk factors. At the time of diagnosis, patients are usually in an impaired physical condition suffering from severe symptoms and advanced functional limitation. In a subgroup of patients, a severe lung vessel disease is present further worsening prognosis. Although in the past few years major improvements in the therapy of some forms of ILD have been achieved, the available drugs are not curative. Their aim remains to slow down disease progression. Therefore, an early detection of ILDs may help to initiate targeted treatment on time and improve the prognosis of patients.

Structural pulmonary changes both due to COPD or ILD result in a loss of small airways and small lung vessels, which are not detectable with standard pulmonary function tests until 50% of the small airways disappeared. Although these changes may also take place due to physiological lung-aging, in smokers this effect is clearly accelerated. Diffusion capacity (DLCO) and the so-called Krogh factor (KCO) are sensible markers of early pulmonary structural changes. In addition, lung density as assessed by high-resolution CT-scan and analyzed by specific software represents a sensitive tool. Pulmonary vascular resistance (PVR) and pulmonary vascular compliance are sensitive parameters for the detection of pulmonary vascular changes.

Similar to DLCO, high fidelity analysis of expiratory CO2-flow measurement may allow a sensitive detection of structural pulmonary changes. The method has the advantage that no extrinsic gas is needed. The aim of this explorative pilot study is to investigate if high fidelity expiratory CO2-analysis is able to detect early pulmonary structural changes, even before it can be assessed by pulmonary function testing (e.g. FEV1 or vital capacity).

Inclusion criteria

• all male and female patients older than 18 years who have COPD, ILD or are smokers and non smokers without pulmonary diseases.
• right heart catheterization performed due to to suspected pulmonary hypertension and further clinical investigation like echocardiography, lung function testing, 6-minute walk test, laboratory testing and blood gas analysis.
• written informed consent

Exclusion criteria

• contraindication for lung function testing
• acute life-threatening disease (including acute myocardiac infarction, pulmonary embolism, large aortic aneurysma, pneumothorax, opthalmic, brain, abdominal or thoracic surgery within the last 4 weeks, hemoptysis).