[Why are the lungs dry?]. / Weshalb ist die Lunge trocken?12.

The extremely thin blood-gas barrier, the high blood perfusion rate and the deformability of the lung required for ventilation call for safety measures in order to keep the peripheral airspaces dry. The protective factors are provided in part by the particular structural organization of the lung, in part by physiological safeguards. Amongst the structural safety factors the extremely low permeability of the alveolar epithelial cell layer, the effective drainage system of interstitial spaces, and the loose connective tissue layers which surround vessels and bronchi, and which can act as transient fluid reservoirs, should be mentioned. The physiologic safety factors include the low hemodynamic pressures in the pulmonary vessels, the high colloid-osmotic pressure of blood, the decrease in perimicrovascular colloid-osmotic pressure on increased transcapillary fluid filtration, the interstitial pressure gradient between peripheral and central parts of the lung, and the minimal mechanical forces acting on the fine lung parenchyma owing to the low surface tensions provided by alveolar surfactant. Whether the active pumping mechanism improving reabsorption of edema fluid is also operative under normal conditions has not yet been clarified.

Structures of pulmonary surfactant films adsorbed to an air-liquid interface in vitro.

Phospholipid films can be preserved in vitro when adsorbed to a solidifiable hypophase. Suspensions of natural surfactant, lipid extract surfactants, and artificial surfactants were added to a sodium alginate solution and filled into a captive bubble surfactometer (CBS). Surfactant film was formed by adsorption to the bubble of the CBS for functional tests. There were no discernible differences in adsorption, film compressibility or minimal surface tension on quasi-static or dynamic compression for films formed in the presence or absence of alginate in the subphase of the bubble. The hypophase-film complex was solidified by adding calcium ions to the suspension with the alginate. The preparations were stained with osmium tetroxide and uranyl acetate for transmission electron microscopy. The most noteworthy findings are: (1) Surfactants do adsorb to the surface of the bubble and form osmiophilic lining layers. Pure DPPC films could not be visualized. (2) A distinct structure of a particular surfactant film depends on the composition and the concentration of surfactant in the bulk phase, and on whether or not the films are compressed after their formation. The films appear heterogeneous, and frequent vesicular and multi-lamellar film segments are seen associated with the interfacial films. These features are seen already upon film formation by adsorption, but multi-lamellar segments are more frequent after film compression. (3) The rate of film formation, its compressibility, and the minimum surface tension achieved on film compression appear to be related to the film structure formed on adsorption, which in turn is related to the concentration of the surfactant suspension from which the film is formed. The osmiophilic surface associated surfactant material seen is likely important for the surface properties and the mechanical stability of the surfactant film at the air-fluid interface.

Effects of fixatives on function of pulmonary surfactant.

The structure of pulmonary surfactant films remains ill defined. Although plausible film fragments have been imaged by electron microscopy, questions about the significance of the findings and even about the true fixability of surfactant films by the usual fixatives glutaraldehyde (GA), osmium tetroxide (OsO(4)), and uranyl acetate (UA) have not been settled. We exposed functioning natural surfactant films to fixatives within a captive bubble surfactometer and analyzed the effect of fixatives on surfactant function. The capacity of surfactant to reach near-zero minimum surface tension on film compression was barely impaired after exposure to GA or OsO(4). Although neither GA nor OsO(4) prevented the surfactant from forming a surface active film, GA increased the equilibrium surface tension to above 30 mN/m, and both GA and OsO(4) decreased film stability as seen in the slowly rising minimum surface tension from 1 to ~5 mN/m in 10 min. In contrast, the effect of UA seriously impaired surface activity in that both adsorption and minimum surface tension were substantially increased. In conclusion, the fixatives tested in this study are not suitable to fix, i.e., to solidify, surfactant films. Evidently, however, OsO(4) and UA may serve as staining agents.

Alveolar surface forces and lung architecture.

The entire alveolar surface is lined by a thin fluid continuum. As a consequence, surface forces at the air-liquid interface are operative, which in part are transmitted to the delicate lung tissue. Morphologic and morphometric analyses of lungs show that the alveolar surface forces exert a moulding effect on alveolar tissue elements. In particular, in lungs at low degrees of inflation, equivalent to the volume range of normal breathing, there is a derecruitment of alveolar surface area with increasing surface tensions which reflects equilibrium configurations of peripheral air spaces where the sum of tissue energy and surface energy is minimum. Thus, changes in surface tension alter the recoil pressure of the lung directly and indirectly by deforming lung tissue and hence changing tissue tensions. However, the interplay between tissue and surface forces is rather complex, and there is a marked volume dependence of the shaping influence of surface forces. With increasing lung volumes the tissue forces transmitted by the fiber scaffold of the lung become the predominant factor of alveolar micromechanics: at lung volumes of 80% total lung capacity or more, the alveolar surface area-volume relation is largely independent of surface tension. Most important, within the range of normal breathing, the surface tension, its variations and the associated variations in surface area are small. The moulding power of surface forces also affects the configuration of capillaries, and hence the microcirculation, of free cellular elements such as the alveolar macrophages beneath the surface lining layer, and of the surfaces of the peripheral airways. Still enigmatic is the coupling mechanism between the fluid continua of alveoli and airways which might also be of importance for alveolar clearance. As to the surface active lining layer of peripheral air spaces, which determines alveolar surface tension, its structure and structure-function relationship are still ill-defined owing to persisting problems of film preservation and fixation. Electron micrographs of alveolar tissue, of lining layers of captive bubbles, and scanning force micrographs of surfactant films transferred on mica plates reveal a complex structural pattern which precludes so far the formulation of an unequivocal hypothesis.

Surface activity in situ, in vivo, and in the captive bubble surfactometer.

For studies of the mechanical effects of lung surfactants, the captive bubble surfactometer (CBS) combines the advantages of the continuous film of Pattle's bubbles with the feasibility of the Langmuir-Wilhelmy balance to produce surface tension-area hysteresis loops. The CBS allows the compression of films to very low and stable surface tensions of 1-2 mN/m. Such low and stable surface tensions are in line with results obtained from pressure-volume studies on excised lungs. In addition, the CBS is useful to test other essential physical properties of the surfactant system, including: (1) rapid film formation (within seconds) through adsorption from the hypophase; (2) low film compressibility with a fall in surface tension to very low (<2 mN/m) values during surface compression; and (3) effective replenishment of the surface film on expansion by the incorporation of surfactant material from material associated with the surface (the surface associated surfactant reservoir). Morphological observations of films fixed in situ or in vitro reveal frequently their multilayered structure, which is consistent with the concept of the surface reservoir. The deviation of the bubbles from a Laplacian shape at very low surface tension and the morphological observations suggest that the surfactant film cannot be considered a simple monolayer.

The lung of the marmoset (Callithrix jacchus): ultrastructure and morphometric data.

Owing to its small size (body weight 300-400 g), its modest demands on animal husbandry, and in particular its relatively long life-span (up to 12 years) the common marmoset (cotton ear marmoset: Callithrix jacchus (Cj)) might be a useful animal model to study the adaptive capacity to different energetic demands, adverse environmental influences such as air pollution, and aging of the lung. In order to describe the gas exchange apparatus of healthy marmosets as a basis for further pulmonary research, the lungs of three young adult animals have been analysed both qualitatively and quantitatively (by morphometry) at the light and electronmicroscopic level. Qualitatively, there is a general similarity in the architecture and structure of lung parenchyma between marmosets and other mammals. Quantitatively, the alveolar surface area was found to be 7662+/-1647 cm(2). Capillary surface area and volume were 6000+/-1549 cm(2), and 1.01+/-0.34 ml, respectively. The harmonic mean thickness of the air-blood barrier was 0.517+/-0.117 microm. These morphometric parameters allowed to estimate the diffusing capacity for oxygen at 0.0299+/-0.0134 ml O(2) (sec mmHg)(-1). In comparison with mammals of similar body size (rats, quinea pigs) it appears that the marmoset has a higher gas exchanging capacity of the lung, which might reflect the 'athletic' activity of this small primate. An incidental finding worth mentioning is the individual variability of septal structures due to variations in capillary blood volume and hematocrit. The distinction between such functional variations and subtle pathologic alterations of lung tissue requires a morphometric analysis at the electron-microscopic level.

Structures of surfactant films: a scanning force microscopy study.

The alveolar lining layer is thought to consist of a continuous duplex layer, i.e., an aqueous hypophase covered by a thin surfactant film which is a monolayer with dipalmitoyl-phosphatidylcholine (DPPC) as its most important component. Findings obtained by electron microscopy and results from in vitro experiments suggest, however, that the structure and hence the structure-function relations of surfactant films are more complex. In order to better define their structures films of surfactants were studied by scanning force microscopy. Four different surfactants were spread on a Langmuir-Wilhelmy balance, and then transferred onto a solid mica plate by the Langmuir-Blodgett technique, under various states of film compression. Imaging of the films by scanning force microscopy was performed in the contact (repulsive) mode in air. The scanning force micrographs revealed that surfactant films are not homogeneous, but rather undergo phase transitions depending on the surface pressures. Even at comparable surface pressures different surfactants show quite different surface patterns. Differences in surface structure can even be observed in films containing surfactant proteins (SP)-B and SP-C. These observations give further evidence that the widely accepted hypothesis of a regular monolayer of phospholipids governing the surface tension probably does not hold true, but that the structure-function relationship of surface active surfactant films is even more complex than hitherto thought.

Formation and structure of surface films: captive bubble surfactometry.

The adsorption model for soluble surfactants has been modified for suspensions of pulmonary surfactant. The dynamic adsorption behavior may be governed by a two-step process: (1) the transfer of molecules between the surface layer and the subsurface layer, which has a thickness of a few molecular diameters only; (2) the exchange of molecules between the subsurface and the bulk solution. The first step is an adsorption process and the second step is a mass transfer process. Between the subsurface and the bulk solution is an undisturbed boundary layer where mass transport occurs by diffusion only. The thickness of this boundary layer may be reduced by stirring. Rapid film formation by adsorption bursts from lipid extract surfactants, as observed in the captive bubble system, suggests that the adsorption process as defined above is accompanied by a relatively large negative change in the free energy. This reduction in the free energy is provided by a configurational change in the association of the specific surfactant proteins and the surfactant lipids during adsorption. The negative change in the free energy during film formation more than compensates for the energy barrier related to the film surface pressure. In the traditional view, the extracellular alveolar lining layer is composed of two parts, an aqueous subphase and a surfactant film, believed to be a monolayer, at the air-water interface. The existence and continuity of the aqueous subphase has recently been demonstrated by Bastacky and coworkers, and a continuous polymorphous film has recently been shown by Bachofen and his associates, using perfusion fixation of rabbit lungs with slight edema. In the present chapter, we have described a fixation technique using a non-aqueous fixation medium of perfluorocarbon and osmium tetroxide to fix the peripheral airspaces of guinea pig lungs. A continuous osmiophilic film which covers the entire alveolar surface, including the pores of Kohn, is demonstrated. By transmission electron microscopy, the surface film frequently appears multilaminated, not only in the alveolar corners or crevices, but also at the thin air-blood barrier above the capillaries. Disk-like structures or multilamellar vesicles appear partially integrated into the planar multilayered film. In corners and crevices, tubular myelin appears closely associated with the surface film. Tubular myelin, however, is not necessary for the generation of a multilaminated film. This is demonstrated in vitro by the fixation for electron microscopy of a film formed from lipid extract surfactant on a captive bubble. Films formed from relatively high surfactant concentration (1 mg/ml of phospholipid) are of variable thickness and frequent multilayers are seen. In contrast, at 0.3 mg/ml, only an amorphous film can be visualized. Although near zero minimum surface tensions can be obtained for both surfactant concentrations, film compressibility and mechanical stability are substantially better at the higher concentrations. This appears to be related to the multilaminated structure of the film formed at the higher concentration.

Influence of bilirubin on surface tension properties of lung surfactant.

AIM: To investigate the influence of bilirubin on the surface tension activity of a porcine derived (Curosurf) and synthetic (Exosurf) surfactant. METHODS: The captive bubble surfactometer at phospholipid doses of 0.5 mg/ml (low dose) and 1 mg/ml (high dose) in solutions of increasing bilirubin concentrations (0.25, 0.5, and 1.0 mg/ml) was used. RESULTS: Curosurf (without bilirubin) showed a higher surface f1p4ion activity than Exosurf, as shown by area compression of 30 (SD 0.6)% compared with 76(1.4)% at low surfactant dose and 25 (0.9)% compared with 85 (0.5)% at high dose (P < 0.01). Bilirubin showed negligible surface activity at the concentrations studied. At low phospholipid dose (0.5 mg/ml Curosurf), bilirubin increased film area compression of lipid extract surfactant from 30 (0.6)% to 55 (1.6)%, 59 (0.1)%, and 68 (0.5)% at the three studied bilirubin concentrations, respectively (P < 0.01). At high phospholipid dose (1 mg/ml Curosurf), bilirubin had the same adverse, although less pronounced, effect on film area compression of porcine lipid extract surfactant (25 (0.9)% vs 26 (0.9)%, 39 (1.3)%, and 44 (1.1)%, respectively) (P < 0.01). Using synthetic surfactant (Exosurf), with a much lower original surface activity, bilirubin did not further inhibit its surface tension properties at any of the phospholipid doses studied. CONCLUSION: These results indicate that in vitro bilirubin impairs the surface tension activity of porcine lipid extract surfactant, but does not affect synthetic surfactant activity.

Lung lesions in experimental hydrostatic pulmonary edema: an electron microscopic and morphometric study.

Distinct barrier lesions and an apical-basal distribution of alveolar edema fluid in either moderate or high elevated pressure edema lungs have been found in previous studies. In the present study, quantitative measurements were obtained by using electron microscopy and morphometry of extravascular lung water and barrier lesions, on the relations between interstitial and alveolar edema fluid as well as between extravascular lung water and barrier lesions. The study further addressed the question of whether 6% bovine serum albumin (BSA) perfusion could induce lung ultrastructure alterations. It was found that interstitial fluid distribution is similar to that of alveolar edema fluid. Epithelial blebs are also distributed with an apical-basal gradient, and are always submerged in alveolar edema fluid. Perfusion with 6% bovine serum albumin does not induce any lung ultrastructure alterations. The results indicate that endothelium and epithelium play a different role in controlling fluid movement between capillary and extravascular spaces and thus in preventing the formation of interstitial and alveolar edema. Because the interaction of cells and tissue must be taken into account, simple physiological models of pulmonary fluid exchange may not be adequate to explain pulmonary edema formation.

Effect of acidosis on bilirubin-lipid extract surfactant interaction.

The risk of bilirubin toxicity in newborn infants with respiratory distress syndrome and hyperbilirubinemia may depend on many factors including pH of the system. Biophysical activity and inhibition characteristics were studied in vitro for lipid extract surfactant (Curosurf, 0.25 mg/ml phospholipids), bilirubin (1.0 mg/ml dissolved in NaOH) and mixed solutions at different pH ranging from 5.0 to 7.4. It was found that unconjugated bilirubin modifies surface tension behavior of lipid extract surfactant films. Maximum and minimum surface tension levels were significantly higher in mixed solutions compared to experiments using pure Curosurf independently from pH. Film area compression for pure Curosurf was not influenced by pH and varied between 22 +/- 4% at pH 5.0 and 23 +/- 9% at pH 7.4. Adding bilirubin to lipid extract surfactant, area compression to achieve minimum surface tension increased significantly to 83 +/- 4% at pH 5.0 and 85 +/- 4% at pH 7.4 (p < 0.01). Bilirubin alone showed negligible surface activity independently from pH (83 +/- 7% at pH 5.0 and 78 +/- 9% at pH 7.4) (p > 0.5). We conclude that bilirubin has a detrimental effect on the surface tension properties of lipid extract surfactant in vitro and that this interaction is independent from pH. These data suggest no influence of acidosis on alveolar surfactant system in babies with respiratory distress syndrome and hyperbilirubinemia.

The surface-associated surfactant reservoir in the alveolar lining.

A small atmospheric bubble was introduced into a surfactant suspension in a captive bubble surfactometer. After film formation to the equilibrium surface tension at the bubble air-liquid interface, the bulk phase surfactant was depleted by replacing the chamber contents several times with a saline-CaCl2 solution. The remaining film adsorbed at the bubble surface was then compressed stepwise in quasi-static fashion to near zero minimum surface tension. This was followed by a series of quasi-static expansion steps to surface tensions slightly above equilibrium. The surface tension of films from lipid extract surfactants and phospholipid mixtures did not increase in a manner consistent with the presence of a single surface monolayer. After the initial, rapid rise in surface tension at each expansion step, a decrease in surface tension to a new value was observed. This decrease in surface tension is likely due to the adsorption of 'surplus' material from a 'surface-associated reservoir' into the surface active film. The presence of surplus non-monolayer surfactant material in situ at the alveolar surface was also demonstrated by electron microscopy. SP-A acted as a potent promoter for the movement of excess material (equivalent to 2-3 monolayers) at the interface into the surface active film. In contrast, inhibitory serum proteins prevented the formation of a surface-associated reservoir or the adsorption of excess material into a surface active film.

Disturbance of alveolar lining layer: effects on alveolar microstructure.

To further study the influence of altered surface tensions on alveolar micromechanics, we analyzed the structure-function relationships in excised rabbit lungs filled with or rinsed by a fluorocarbon (approximately 15 mN/m) or by hexadecane (approximately 25 mN/m). The lungs were fixed and dehydrated by vascular perfusion, and the tissue samples were analyzed by light, transmission, and scanning electron microscopy. We made three observations. 1) Pressure-volume (P-V) loops hexadecane-filled lungs are shifted to the left and coincide with those of saline-filled lungs, indicating near-zero interfacial tension. In accordance, the alveolar microstructure and surface area of hexadecane-filled lungs resemble those of saline-filled lungs. 2) The P-V loops of fluorocarbon-filled lungs are not shifted to the left but coincide with those of fluorocarbon-rinsed lungs. Under both conditions, the alveolar microstructure is qualitatively identical and the alveolar surface areas are markedly reduced compared with normal air-filled lungs. These findings show that fluorocarbon-filled or fluorocarbon-rinsed lungs are subjected to similar interfacial tensions at the alveolar level. 3) Hexadecane-rinsed lungs show a pear-shaped P-V curve and a complex surface texture of peripheral air spaces. These results, together with in vitro observations, suggest a metamorphic interplay between lung surfactant and hexadecane in lining the surface and determining the surface tension. Evidently, the effects of foreign liquids introduced into the lung on the structure-function relationship cannot accurately be predicted from their in vitro surface tensions. This fact should be considered in the development of artificial surfactants.

[Diagnosis bronchial carcinoma: therapeutic decisions]. / Diagnose Bronchuskarzinom: therapeutische Entscheide.

Decisions about the best management of chest malignancies often are not black-and-white decisions, but have to be taken in grey areas. In order to be aware of all treatment options and to appropriately weigh the profits and risks of treatment, the evaluation should be done by a teamwork of all specialists who can provide possible therapeutic benefit to the patient. In addition, it is a prerequisite that the informed patient and his primary care physician are fully involved in the collaborative treatment plan decided on.

Bronchial reactivity to isocapnic hyperventilation: results in an unselected population of outpatients with known or suspected asthma.

Isocapnic hyperventilation with dry air is nearly as effective as with dry cold air, and appears to be a valuable screening test for bronchial hyperresponsiveness. However some incidental factors such as prechallenge bronchoconstriction, level of hyperventilation, age and smoking habits have barely been examined or were investigated in small samples of either normals or well-characterised asthmatics. In an inhomogeneous population of 186 outpatients with known asthma, 286 with suspected asthma and 32 normals, a single isocapnic hyperventilation challenge of 6-min duration was performed. There was a weak, but significant correlation between the degree of prechallenge airway function and the bronchial response, assessed by the change in forced expiratory volume in 1 s (r = 0.27, p = 0.000) in known asthmatics, but not in patients with suspected asthma and in normals. No significant relation was found between the level of hyperventilation and the bronchial response when comparing the bronchial response to the single-dose hyperventilation test between the subjects (NS). Increasing age appears to be associated with an attenuation of the response in known asthmatics (r = 0.21, p = 0.004), but not in patients with suspected asthma. Smoking habits did not affect the bronchial response in this study. In conclusion, the main finding is that there is a weak correlation between baseline airway obstruction and the subsequent response to isocapnic hyperventilation, a slow decline in response with age and no increase in responsiveness in smokers. Hence, isocapnic hyperventilation is a relatively robust test for assessing bronchial reactivity in an inhomogeneous population of outpatients like ours.

Experimental hydrostatic pulmonary edema in rabbit lungs. Morphology.

To study the accumulation and distribution of edema fluid and the associated changes in alveolar microarchitecture, edema was induced in excised rabbit lungs perfused with 6% albumin solution. The lungs, including the edema fluid, were then fixed by vascular perfusion with glutaraldehyde, osmium tetroxide, and uranyl acetate. Tissue samples were analyzed by light microscopy and transmission and scanning electron microscopy. We found (1) fixation was successful in that the albumin in the edema fluid formed coherent webs indicating the location and arrangement of the extravascular fluid accumulations; (2) regardless of the filtration pressure (about 29 mm Hg in one set of experiments and about 14 mm Hg in the other), an apical to basal gradient of fluid accumulation was found. This gradient was absent in lungs held in the inverse position, suggesting that the regional distribution of pulmonary edema is not simply gravity dependent. At the same lung height, there was a remarkable inhomogeneity of interstitial and alveolar edema. (3) Both the inhomogeneous distribution of fluid and the resulting changes in surface tension affected the entire alveolar architecture. (4) Within interstitial and alveolar spaces, there were striking inequalities in the density of the proteinaceous fluid pools that suggest local differences in the sieving properties of the barriers, that is, in the reflection coefficients for albumin. In conclusion, our findings suggest that the formation of pulmonary edema cannot be explained solely by uniform membrane models for fluid exchange.

Experimental hydrostatic pulmonary edema in rabbit lungs. Barrier lesions.

In excised rabbit lungs perfused with a 6% albumin solution, hydrostatic pulmonary edema was induced by moderate (about 14 mm Hg) and high increases (about 29 mm Hg) of capillary transmural pressure. Thereafter, lung tissue and proteinaceous edema fluid were fixed by vascular perfusion and analyzed by electron microscopy for possible lesions of the blood-gas barrier. The following observations appear noteworthy: (1) There were distinct and numerous lesions of the epithelial cell layer. In high-pressure edema, frank disruptions on the thin and thick sides of the blood-gas barrier were prominent. In moderate pressure edema epithelial blebs were more conspicuous. (2) In contrast, endothelial lesions were rare in both high- and moderate-pressure experiments. (3) Epithelial Type I cells revealed an enormous plasticity as illustrated by the formation of large epithelial blebs. (4) Although the entire microvasculature was subjected to high pressures, barrier lesions were exclusively seen in regions with alveolar edema. These findings suggest that barrier leaks play a role in both hydrostatic and permeability lung edema and that the differences between both types of edema rather reflects the type and extent of injury to the alveolar epithelial barrier and the associated inflammatory reaction.

[Air pollution]. / Luftverschmutzung.

This review includes a summary of the symposium "Air Pollution" of the Swiss Society of Pneumology, and supplementary information on in- and outdoor air quality in Switzerland. With regard to atmospheric pollution, high exposures to ozone during summer are of major concern. A substantial reduction of ozone levels appears to be considerable problem in view of the high population and particular topography. More precise estimates of possible health damage require further epidemiological studies. In this context it is interesting to note that the environmental catastrophe of Kuwait did not reveal new insights into the dose-effect relation of air pollutants, in that the exposure of the population and hence the health hazards of oil fires were less serious than expected. As to the wellbeing of humans, indoor air pollution deserves equal attention. The predominant noxious agent is tobacco smoke, which significantly affects the respiratory health of infants. In addition, there is some epidemiological evidence that passive smoking can cause lung cancer. However, a variety of other and often neglected pollutants can be present in homes and at workplaces and may be the cause of various respiratory diseases. Finally, thought is given to more general problems such as better definitions and diagnosis of diseases due to airborne agents, the cost-benefit ratio and the conflicts of interest involved in effective control measures.

[Chronic asthmatic bronchitis]. / Chronische Asthmabronchitis.

Many patients with chronic obstructive pulmonary disease (COPD) episodically or continuously have asthmatic signs with a degree of reversibility in response to bronchodilators. In such cases, the diagnosis 'chronic asthmatic bronchitis' is often used, although the cause-effect relationship between COPD and asthmatic manifestations is not established. Hence, the 'chronic asthmatic bronchitis' is not a pathogenetic diagnosis, but rather a working diagnosis which implies a specific treatment of the reversible component of chronic airway obstruction. Certainly, the most important measure to avoid a rapid progression of COPD is the elimination of damaging agents by inhalation (smoking). In addition, it was a widely accepted belief that these patients require a continuous inhalation therapy with beta-agonists or anticholinergics. However, there is new evidence, indicating that a continuous treatment might accelerate the decline in ventilatory function and that a better long-term outcome might be achieved by on-demand inhalations.

[New aspects of asthma therapy]. / Neue Aspekte in der Asthmatherapie.

Until recently, optimal bronchodilatation and in particular the inhalation of beta-agonists was considered the mainstay of asthma therapy. Steroids were added only in case of an unsatisfactory treatment effect. Recent epidemiological surveys, revealing an association between asthma mortality and the use of beta-agonists, and well controlled treatment studies suggest a change of concepts. Considering the long-term course of asthma, early suppression of asthmatic airway inflammation appears to be at least as important as an effective bronchodilatation. A prerequisite for a success of an individually taylored pharmacologic treatment is a comprehensive management of the disease, inclusive a continuous patient education.