European journal of respiratory diseases. Supplement最新文献

Several techniques for the study of human airway epithelial ion transport employing cultured cells were explored. Human nasal epithelial cells were cultured in serum-free, hormone supplemented media. For bioelectric characterization of ion transport functions of cultured cells, cells were inoculated into heterologous grafts, and implanted into immunocompromised mice, or onto collagen membranes maintained in vitro. Cells populating either preparation exhibited a pattern of Na+ and Cl- transport similar to that of freshly excised nasal specimens. Differences between preparations were observed for absolute transport rates, tissue resistance, and morphology. We conclude that (1) cell culture techniques will be useful in investigating ion transport activities of human pulmonary epithelia from normal and abnormal lungs; and (2) the selection of specific culture techniques should be guided by the nature of the epithelial functions tested.

A panel of monoclonal antibodies, detecting different intermediate sized filament proteins, was prospectively applied on all specimens derived from S.C.L.C. patients attending our clinic in 1985. Reactivity with the antibodies was subsequently correlated to clinical data. The results indicate a heterogeneous pattern of reactivity of the assessed antibodies. However this heterogeneity is not a straightforward extension of the intermediate sized filament expression in SCLC cell lines.

It can be stated that, depending on the type of lung cancer, the best opportunity for curative treatment is in the early stage of disease, when cancer is limited to the lung and surgical intervention can be indicated. Especially in the case of SCLC, the number of patients presenting with such a limited disease is very low. In SCLC, chemo- and/or radiotherapy can induce initial good responses, which, although not curative in most cases, can elongate life for an average of 10 months. Although changes and refinements in treatment are continuously introduced, further progresses in the outcome have not achieved for the last decennium. Therefore, more fundamental research is needed to indicate new treatment avenues. A number of findings appear promising in this field. Firstly, the development of tissue culture techniques has enabled a better study of the biological properties of both SCLC and non-SCLC. Secondly, the development of monoclonal antibodies has refined the possibilities to type lung cancer. Particularly if monoclonal antibodies could be identified which occurrence turns out to be relevant to prognosis, immunohistopathology could become an important additional tool for the assessment of a pathological diagnosis in lung cancer. In addition, monoclonal antibodies which are specific for lung cancer could be used for an immunotherapeutical approach in the near future. Such a treatment might complement currently available treatment modalities.

Mucus hypersecretion (greater than 25 ml/day) is commonly seen in chronic bronchitis, whereas bronchorrhea (greater than 100 ml/day) is found in other conditions (e.g. asthma, bronchiectasis, alveolar-cell carcinoma). Clearance of secretions can be improved by physical and pharmacological methods. Cough airways obstruction--for "two-phase air-liquid flow". Chest physiotherapy (the forced expiration technique, FET, and postural drainage, PD) is effective in clearing central and peripheral secretions and can be self-employed. Oral high frequency oscillation (OHFO) at 13 Hz is a useful adjunct. Beta-adrenergic drugs improve clearance and this is not entirely to their bronchodilator activity. Likewise methylxanthines enhance clearance particularly in central airways. Corticosteroids are effective in bronchorrhoea and asthma. Anticholinergics may control hypersecretion. Mucolytics and expectorants are used traditionally but their activity is difficult to prove. Hypertonic (7%) saline is useful--as is cromoglycate in asthma.

Tracheobronchial mucociliary clearance was measured in 37 patients with early simple chronic bronchitis. A non-invasive radio-aerosol technique with inhalation of 99Tcm labelled 5-microns polystyrene particles followed by assessment of radio-nuclide distribution by posterior gamma-camera scans was employed. The mucociliary clearance of the bronchitics was significantly lower than clearance of a non-smoker control group. An interim analysis of the effect of treatment with a surfactant stimulating drug, ambroxol, suggested a dosage-dependent tendency to a faster mucociliary clearance than seen in placebo-treated bronchitics.

The anatomy and physiology of the pulmonary epithelial barrier are briefly described, and methods of measuring permeability of the barrier to solutes are outlined, including findings on alveolar barrier permeability to 99mTcDTPA. A method for measuring permeability to 99mTcDTPA of the conducting airways is described in which the effect of mucociliary clearance can be quantified using radio-labelled polystyrene microspheres 5 mum in diameter. When the 99mTcDTPA clearance rates from inner, intermediate and outer zones of the lungs are corrected fro the effect of mucociliary clearance, there is a significantly slower clearance from the conducting airways than from the alveoli.

The aim of this series of studies was to investigate the quality and quantity of farmers' exposure to airborne spores during the handling of hay or grain. In the beginning, the Petri dish method and later a six-stage Andersen sampler were used to collect the samples. The number of spores of mesophilic fungi, thermotolerant fungi, thermophilic actinomycetes and fungi of the Aspergillus glaucus group were determined in order to find possible causative agents of farmer's lung disease. The level of exposure varied from 10(4) cfu/m3 to 10(7) cfu/m3 (cfu = colony forming unit). In hay, fungi of the A. glaucus group usually dominated. In grain the most common moulds were Cladosporium spp. and Penicillium spp. In both hay and grain the most common thermophilic actinomycete was Thermoactinomyces vulgaris; Micropolyspora faeni was found less frequently. Silaging was found to be the best method to prevent moulding of hay. Chemicals added during baling did not satisfactorily prevent moulding of hay. For stored grain, however, the best results were obtained with propionic acid treatment. The quality and quantity of airborne spores found suggests that farm work exposes farmers to a high risk of becoming sensitized, which leads to the development of asthma or farmer's lung. Few of the methods presently available for making or storing hay and grain can satisfactorily prevent moulding. So far, use of personal dust respirators with a type P2 (previously II b) filter seems to be the only way to effectively diminish exposure to spores.

Previous studies of the mechanisms of killing of inhaled bacteria have been confined to the demonstration that alveolar macrophages phagocytose and kill inhaled staphylococcus intracellularly. We have found recently th at the surfactant-containing fraction of rat bronchoalveolar lavage fluid is bactericidal for pneumococci and some other gram-positive bacteria, excluding staphylococci. In studies reviewed herein, we show that these antibacterial factors in rat surfactant are long-chain free fatty acids (FFA). Polyunsaturated FFA appear to be particularly active. Because inhaled pneumococci are cleared very rapidly in vivo in the absence of conventional opsonins, we speculate that FFA may have a rôle in pneumococcal killing. All species tested to date, including humans, dogs, and guinea pigs have detectable FFA in their surfactant, although the level of FFA in these species is lower than in rats. Human and guinea pig surfactant, in fact, have too little FFA in their pulmonary surfactant to give detectable antipneumococcal activity in vitro. Nonetheless, inhaled pneumococci are killed rapidly by guinea pigs, suggesting that the level of FFA in bronchoalveolar lavage is not a good indication of the amount of FFA on alveolar surfaces, or, alternatively that FFA may not play a rôle in pneumococcal clearance in vivo. We have recently completed histological studies which demonstrate that inhaled pneumococci are, in fact, killed extracellularly in rats. This observation adds credence to the concept that mechanisms exist in the alveoli for extracellular killing of some bacteria and indicates that further studies of FFA in this process are worthwhile.