[Chronic bronchitis, COPD]. / Chronische Bronchitis, COPD.

Chronic bronchitis is part and precursor of COPD, a complex disease triggered mostly by exposure to cigarette smoke. However COPD develops only in patients with specific susceptibility probably determined by genetic factors or additional risk factors. A specific type of inflammation resides in the bronchial and bronchiolar walls, that infers damage not only to airway structure but also to surrounding alveolar attachments and thus to the lung parenchyma. Chronic bronchitis, fibrosing bronchiolitis and emphysema constitute the three main stems of pathology of the disease but may coexist with varying extent. The clinical picture is therefore quite variable. Treatment exists largely in bronchodilation combining different mechanisms and using long acting drugs usually applied by inhalation. Acute exacerbations promote progression of the disease, which must be counteracted by adaptation and intensification of therapy, in some cases including non invasive or invasive ventilation. Several non-pharmacologic measures such as smoking cessation, rehabilitation, nutritional support, long term oxygen therapy, lung volume reduction and possibly lung transplantation may be available for appropriate patients and have to be considered.

[Effect of ambroxol on surfactant secretion and synthesis in isolated type II alveolar cells]. / Effekt von Ambroxol auf die Surfactantsekretion und -synthese von isolierten, alveolären Typ-II-Zellen.

The effect of ambroxol is attributed in part to an effect on surfactant synthesis and secretion. Evidence supporting this hypothesis is largely indirect; a direct effect of ambroxol on surfactant synthesis and secretion remains to be demonstrated. In this study a direct effect of ambroxol was evaluated using isolated alveolar type II cells. Secretion of labelled phosphatidylcholine was measured following the addition of increasing concentrations (10(-8) M to 10(-4) M) of ambroxol to the culture medium for increasing time intervals. There was no significant increase in surfactant secretion with increased ambroxol concentration or prolonged exposure time. Uptake of 3H-choline and synthesis into 3H-phosphatidylcholine was analyzed as an indicator of surfactant synthesis. Again, increasing concentrations of ambroxol (10(-7) M to 10(-5) M) were followed for 1, 2, 4, 8 and 24 h. There was no significant effect on synthesis at any time point. Concentrations higher than those mentioned here resulted in LDH release from cultured cells. Ambroxol which also has anti-oxidative and anti-inflammatory effects does not exhibit direct stimulatory effects on surfactant synthesis and secretion in isolated (rat) alveolar type II cells as has been demonstrated e.g. for beta 2-adrenergic stimulation. A specific pharmacologic way to stimulate the surfactant system remains to be developed.

The effects of mechanical forces on lung functions.

The lung is a dynamic organ that is subjected to mechanical forces throughout development and adult life. This review article addresses the types of mechanical forces in the lung and their effects on development and normal lung functions. The effects of mechanical forces on the various different cell types of the lung are discussed, as are the mechanisms underlying mechanotransduction.

Acute influence of cigarette smoke on secretion of pulmonary surfactant in rat alveolar type II cells in culture.

It has been shown, that smoking results in a lower yield of surfactant associated phospholipids in bronchoalveolar lavage (BAL). Indirect evidence suggests impaired secretion. In the present study, we investigated the influence of cigarette smoke on surfactant secretion in cultured rat alveolar type II cells. Smoke exposure was achieved by bubbling the smoke of four cigarettes through Dulbecco's modified Eagle's medium (DMEM) which was adjusted to a reference absorption value of 1.36 at 320 nm. Cells were preincubated with various dilutions of cigarette smoke-treated medium for 30 min, and were then exposed to this medium for 2 h. After this time, secretion of 3H-choline-labelled phosphatidylcholine (PC) was measured as a marker of surfactant secretion. A 10 fold dilution of cigarette smoke-treated medium inhibited PC secretion stimulated by a combination of terbutaline, adenosine triphosphate and 12-O-tetradecanoylphorbol-13-acetate by over 50%, but did not alter basal secretion. Exposure to less concentrated cigarette smoke-treated medium resulted in less inhibition. Cellular injury was not observed with the concentrations of cigarette smoke-treated medium used in this study. The gas phase of cigarette smoke was not inhibitory at comparable concentrations. Longer exposure to cigarette smoke-treated medium resulted in increased inhibition of PC secretion. The cigarette smoke ingredients, nicotine and benzo[a]pyrene, failed to inhibit PC secretion. Secretion of type II cells exposed to cigarette smoke-treated medium at lower temperatures was not affected. Addition of antioxidants to medium and cells during the preincubation and secretion period did not alter cigarette smoke-treated medium-induced inhibition of stimulated PC secretion. These results demonstrate a direct inhibitory effect of cigarette smoke constituents on surfactant secretion in type II cells. Inhibition is mediated by compounds contained predominantly in the particulate phase of cigarette smoke. Inactivation of the inhibitory effect by lower temperatures suggests involvement of processes such as enzymatic bioactivation or active transport mechanisms.

Calcium mobilization and exocytosis after one mechanical stretch of lung epithelial cells.

Deep inflation of the lung stimulates surfactant secretion by unknown mechanisms. The hypothesis that mechanical distension directly stimulates type II cells to secrete surfactant was tested by stretching type II cells cultured on silastic membranes. The intracellular Ca2+ concentration was measured in single cells, before and after stretching. A single stretch of alveolar type II cells caused a transient (less than 60 seconds) increase in cytosolic Ca2+ followed by a sustained (15 to 30 minutes) stimulation of surfactant secretion. Both Ca2+ mobilization and exocytosis exhibited dose-dependence to the magnitude of the stretch-stimulus. Thus, mechanical factors can trigger complex cellular events in nonneuron, nonmuscle cells and may be involved in regulating normal lung functions.