European journal of respiratory diseases. Supplement最新文献

Normally the daily volume of lower respiratory tract secretions, in man, is probably less than 100 ml. In hypersecretory disease the volume increases sufficiently to cause cough and expectoration of secretions as sputum. The proportions which are sol or gel vary in disease as does the way in which constituent molecules partition in each phase. The constituent molecules and the cells which produce them (indicated in parentheses) may be classified as follows: 1. Mucus-glycoproteins present as droplets, or sheets (produced by mucous cells), periciliary fluid (serous or ciliated cell or a transudate), surface muco-substance (all epithelial cells) or surfactant hypophase (Clara or type II alveolar cells). 2. Proteins and peptides such as lysozyme (serous cell and macrophage), lactoferrin (serous cell and neutrophil), secretory piece (surface epithelium and submucosal glands), regulatory neuropeptides (dense-core granulated cell and both motor and sensory nerves) and fibronectin (alveolar macrophages). 3. Glycosaminoglycans such as heparan sulphate (epithelial membranes), heparin (mast cell), chondroitin sulphates and hyaluronate (connective tissue constituents). 4. Lipids including triglycerides (stored in cells) glycolipids (cell membrane), phospholipids (type II alveolar cells), sphingolipids (cell membrane), steroids (? Clara cells) and terpenes (cell membrane). 5. Anti-proteases and anti-oxidants such as bronchial protease inhibitors (serous anc Clara cells), alpha-2-macroglobulin (macrophage), alpha-1-antitrypsin (transudate) and anti-oxidants (type II alveolar cell and macrophage). 6. Other 'secretions' including ions and water (surface epithelium and submucosal glands), mediators of inflammation (migratory cell granules and their membranes), and serum proteins (present in transudate/exudate).

The predominant cause of mucus hypersecretion in Westernized countries is smoking. Mucus hypersecretion in smokers is correlated with the subsequent development of bronchial carcinoma but there is no definite causal relation to progressive airflow obstruction. The distinction between hypersecretion and the development of airflow obstruction may also be relevant in childhood and occupational respiratory disease. Endogenous factors may also be important, as suggested by the increased prevalence of hypersecretion in asthma, but are difficult to detect by epidemiological techniques.

The major pharmacodynamic actions of ambroxol are surfactant stimulation, mucokinetic and secretagogue activity. The therapeutic activities of the drug in animal models of the infant and adult respiratory distress syndrome (IRDS and ARDS) are reviewed. SO2 exposed rats, which exhibited increased airway resistance and work of breathing, were used as an animal model of a bronchitic syndrome. The active group was treated with 25 mg kg-1 oral ambroxol for 10 days. The airway resistance of this group (53.6 +/- 7.0 Pa.ml-1.s) was significantly lower than that of the control (81.2 +/- 11.4). Specific work of breathing was also lower in the treated group (0.26 +/- 0.02 mJ.ml-1, control: 0.35 +/- 0.029). The alleviation of airflow limitation was a consequence of subacute treatment and not of acute bronchodilatation. Treatment with the beta 2-adrenergic drug clenbuterol further improved both active and placebo groups.

This study was based on data provided by 9,483 farmers from a larger sample of 12,056 Finnish farmers. The data were collected in two postal surveys, with a 3-year interval between them, conducted by the Social Insurance Institution of Finland. About one-third of the whole population were smokers. Among men the prevalence of smoking was 58.6% and among women 10.2%. Among men the prevalence of smokers was larger in older groups, among women the situation was reversed. Based on past or present infantile eczema, atopic dermatitis, or allergic rhinitis, one-third of the subjects were classified as atopic. The prevalence of atopy was essentially the same in all age groups. The prevalence of chronic bronchitis was 8.0%, and the mean annual incidence was 2,017 per 100,000 farmers. Among farmers who tended cattle the prevalence of farmer's lung was 1.7% and the mean annual incidence was 540 per 100,000 similar farmers. Chronic bronchitis was twice as common among atopic as among non-atopic subjects and twice as common among smokers as among non-smokers. Atopy and smoking seemed to have an additive effect on both the prevalence and incidence of chronic bronchitis. The results strongly support the so-called "Dutch hypothesis" about the natural history of chronic bronchitis, according to which chronic bronchitis is closely related to asthma. Farmer's lung was only slightly more common among atopic than among non-atopic subjects and twice as common among non-smokers as among smokers.

With several variables, such as patient or subject, disease, surroundings, machine and personnel, it is a wonder that successful epidemiological studies using lung function parameters can be done at all.

Excessive bronchial secretions within the airways can be transported by two-phase gas-liquid flow with airflow rates encountered during normal tidal breathing. The transport speed of secretions with this mechanism is as effective as the mucus clearance rate in normal subjects. The thickness of bronchial secretions required to effect two-phase gas-liquid flow is about 10% of the airways diameter which is not an unusual situation for patients who have bronchial hypersecretion. Periodic airflow as encountered in normal breathing is more effective than continuous flow in moving secretions in one direction or another. However, to propel the secretions toward the larynx, expiratory airflow velocity should be higher than inspiratory airflow velocity. This pattern can be achieved by imposing a controlled pattern of mechanical ventilation and is also probably the basis for the "huffing manoeuvre" taught by chest physiotherapists to clear airway secretions. Increased elasticity and decreased viscosity of secretions promote higher transport rates by two-phase gas-liquid flow. Conditions for two-phase gas-liquid flow during tidal breathing can be met at the 8th to 9th generation of the airways.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Various inhaled or administered compounds have adverse effects on the surfactant system. In experimental animals quartz inhalation induces alveolar proteinosis. This condition may also be induced by amphiphilic drugs or through increases in surfactant apoproteins. In one experimental model, damage to Clara cells by a methyl-furan derivative led to an increase in extracellular surfactant levels without a change in whole lung pool size. A comparative study of the effects of nitrogen dioxide in the rat and hamster demonstrated differing effects on Clara cells, type II and surfactant levels. These and other studies demonstrate that the effects of chemicals and drugs on cells involved in surfactant synthesis, secretion and catabolism provide a sensitive indicator of incipient toxic effects in the lung.