Lung function and lung diseases
Chronic lung disease
Chronic lung diseases such as Bronchitis, COPD (Chronic obstructive pulmonary disease) or fibrosis or conditions with impaired lung function such as trauma, sepsis, or cystic fibrosis are among the most serious health problems. Lung diseases are responsible for about one-sixth of all deaths worldwide, alone 600.000 people per year in the EU. Thus, they are not only a serious human burden but with - conservatively estimated - 380 billion Euro total cost per year they are also a serious socio-economic burden (Article Lung and Health in Europe). Today it is proven that the lung epithelium which acts as a barrier between air and tissue/blood has a significant role in the pathogenesis of many chronic pulmonary diseases.
The respiratory epithelium is composed of alveoli (air sacs) and the afferent airways. Both areas play a significant role for pathogenetic processes associated with (-> Link) Lung Remodeling, although the result may be different: emphysema in terms of tissue loss and fibrosis in terms of tissue excess. Alveolar epithelium produces surfactant, a lipid-rich, lipoprotein-like substance, and separates them by exocytosis into the interior (lumen) of the alveoli, called surfactant secretion.
Surfactant forms a thin lipid layer at the air-liquid interface (ALI), which protect the alveoli from collapsing by reducing the surface tension. Surfactant contains specific proteins whose importance is increasingly recognized for the pathogenesis of lung remodeling. Local or systemic malfunction of the alveolar epithelium and surfactant system can e.g. cause ventilation-induced lesions and inflammatory responses which yield a fibrotic remodeling on the long term. The concept of mechanical microtrauma or an inadequate expansion stress of the epithelium, which is caused by dysfunction of molecular components of the alveoli, is becoming increasingly important.
Increasing experimental evidence also indicates that the ability of the epithelium to resorb alveolar fluid of the alveoli influences these processes. The transepithelial transport of liquid is mediated by the ion channels ENaC (Na +) and CFTR (for Cl-). Another recently identified channel (P2X4) in type II pneumocytes, could also play an important role in alveolar liquid clearance under pathophysiological conditions (ATP release from damaged cells). On the other hand, chronic inflammatory reactions, that are associated with a strong macrophage activation, can yield the loss of alveolar epithelium and thus a decrease in the gas exchange surface and ultimately to emphysema; this is due to the release of elastase and other tissue-dissolving enzymes. Emphysema is the long-standing result of COPD and yields - in addition to disorders of ventilation - a significant diffusion disorder.
Gas and blood analysis and oxidative and nitrosative stress
The lung has a special role in the the release of reactive oxygen species (ROS) and nitrogen species (RNS): oxidative and nitrosative stress – induced by increased formation of ROS and RNS - are considered as a key factor for both chronic diseases such as COPD, atherosclerosis and diabetes and acute stress conditions such as trauma, haemorrhage and sepsis. The presence of an acute respiratory failure (Acute Respiratory Distress Syndrome, ARDS) also determines the prognosis of such acute life-threatening diseases.
Any direct damage of the lung leads to increased production of ROS and RNS or triggers local and systemic inflammatory reactions. The entire heart-minute-volume passes through the lungs, such that the composition of the exhalation gas is a representative perfusion weighted average of the release of these molecules. Finally, the composition of the exhalation gas can be used diagnostically: the enrichment of the 13CO2 / 12CO2 isotope allows the quantification of metabolic processes of the whole organism or - if the right marker label is chosen – of individual organs (e.g. the liver).