Deactivation of the pulmonary surfactant dynamics by toxic aerosols and gases.

Interactions between selected toxic aerosols and gases occurring in the air at the workplace and the pulmonary surfactant (PS) have been studied with two physicochemical techniques in vitro. The Pulsating Bubble Surfactometer (PBS) and the Langmuir-Wilhelmy Balance (LWB) have been used for measurements of dynamic interfacial properties of the PS material after its contact with several gases (sulfur dioxide, nitrogen oxides, ozone, ammonia) and liquids (sulfuric, nitric and hydrochloric acids and ammonium hydroxide), which can be brought into the alveoli with the inhaled air. Surface tension-area relationships for the interface oscillations have been analyzed using qualitative criteria of normalized hysteresis area (HA(N)) and minimum surface tension (sigma(min)). It was demonstrated that, for each analyzed compound, inactivation of the surfactant occurs, but the critical concentrations and doses are compound specific, which suggests the toxic potential of the investigated substances with respect to PS. Possible mechanisms of the interactions between the investigated substances and the surfactant components are discussed. Degradation of the PS dynamical interfacial properties (HA(N) and sigma(min)), important from the physiological viewpoint, observed in our in vitro experiments, suggests a possibility of adverse health effect in the case of a chronic inhalation of toxic gases and aerosols, even at low concentration or after a short exposure to strongly contaminated air. It results in a slowdown of the pulmonary clearance rate and increase of the lung burden for both considered cases.

Deposition and retention of ultrafine aerosol particles in the human respiratory system. Normal and pathological cases.

The particle number concentration in ambient air is dominated by nanometer-sized particles. Recent epidemiological studies report an association between the presence of nanoparticles in inhaled air at the workplace and acute morbidity and even mortality in the elderly. A theoretical model of deposition of 20 nm particles in the human alveolus was formulated. Gas flow structure and deposition rate were calculated for alveoli with different elastic properties of lung tissue. Data obtained in the paper show increased convective effects and diffusional rate of deposition of nanoparticles for alveoli with higher stiffness of the alveolar wall. The retention of deposited particles is also higher in these pathological alveoli. Results of our calculations indicate a possibility of existence of a positive loop of coupling in deposition and retention of nanoparticles in the lung with pathological changes.

Pulse nebulization in pneumatic devices.

Aerosols of a physiological salt solution and aqueous solutions of salbutamol, sodium cromoglicate, and dornase alfa were generated in a pneumatic nebulizer and analyzed in a system with controlled humidity of air as a carrier gas. Mass distribution of aerosol particles and yield of generation for pulse nebulization were measured. Pulsation of generation was realized with an attachment maintained by a computer program. Opening times of the valve were in the range 50-800 ms. The results indicate the possibility of improving aerosol particle delivery to the lung using a pulse generation system.

[Comparative studies of particle distribution range of aerosol cromolyn sodium generated by MDI systems]. / Badania porównawcze rozkladów wielkosci czastek aerozolowych kromoglikanu dwusodowego generowanych z dozowników MDI.

Particles size distribution of the sodium cromoglycate preparations: CROPOZ PLUS and CROMOGEN EB generated with MDI and for under-pressure releasing methods were measured. Results of measurements indicate a significant repeatability of each sample properties. An average contribution of mass of the respirable fraction for both aerosolized pharmaceuticals is in the range of 40% of the generated dose. CROMOGEN EB with optimizer (spacer) gives a higher contribution of the respirable fraction--up to 50% of dose, with simultaneous lower value of the released mass of aerosol. Particles size distribution of CROPOZ PLUS within a respirable fraction indicates an efficient penetration and deposition of particles in the upper, central and peripheral parts of tracheobronchial tree (TB). High contribution of submicron particles of CROMOGEN EB with optimizer gives efficient penetration and deposition of these particles in the lungs.

Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2.

RATIONALE AND OBJECTIVES: Perfluorocarbon (PFC) aerosols present the opportunity for simultaneous analysis of lung structure and pulmonary oxygenation patterns. The authors investigated techniques to nebulize neat liquid PFCs for inhalation as a new method of PFC administration and tested the hypothesis that PFC aerosols may be developed for efficient delivery to the lung in an experimental rat model allowing the potential for sequential monitoring of pulmonary status via quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen (pO2) imaging. METHODS: Pneumatic aerosol generators were configured to produce a neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon inhalation breathing protocols for the rat model included: spontaneous direct breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal breathing. The PFC aerosol delivery into the rat lung was documented through 19F MR imaging in correlation with high-resolution anatomic proton MR images. Theoretical model calculations for PFC mass deposition were compared with experimental results. RESULTS: The pneumatic generator produced a PFC aerosol droplet within the theoretically targeted range (geometric mean particle diameter of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No measurable aerosol reached the lungs during spontaneous breathing because of the efficient filtering capabilities of the turbinated nasal passages. With tracheotomy, aerosol depositions within the lung were achieved in mass quantities consistent with theoretical expectations; however, the distribution patterns were nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated. CONCLUSIONS: Perfluorocarbon aerosols of controlled size distribution can be produced at sufficient concentration with pneumatic generators for distribution to the terminal pulmonary architecture and visualization using 19F MR imaging. The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system and development of sophisticated experimental animal models of systemic oxygen transport as a function of pulmonary status.

Displacement of alveolar macrophages in air space of human lung.

The role of alveolar macrophages in the process of the human lung clearance is summarised. Three patterns of alveolar macrophage (AM) displacement on the surface of alveolus are distinguished depending on the loading of the surface with insoluble deposits, i.e. directional, directional with small stochastic noise and purely random. The physical analysis is presented of chemotactic movement and hydrodynamical effects on the residence time of AMs in a geometrical model of the human alveolus. The calculation of exit times from the alveolus is also presented. Calculations show that simultaneous passive and active displacement of AMs loaded with particles reduces exit time of the macrophage by 85%, compared to the case of purely directional movement. When active transport is reduced, due to AM overloading, exit time is determined by the passive transport rate. For reduced surfactant activity, the exit time of AM from the alveolus is the function of its chemotactic activity only and is inversely proportional to AM mobility. The exit time of AMs tends towards infinity when both mechanisms of clearance decay.

An improved mathematical model of hydrodynamical self-cleansing of pulmonary alveoli.

In the present paper we postulate a hydrodynamical mechanism of pulmonary alveoli cleansing and explain the role of the lung surfactant system in this phenomenon. Then a new, significantly refined mathematical model of the dynamics of the layer lining alveoli is derived and tested numerically in order to check theoretically whether the mechanism postulated can explain the phenomenon observed and to establish the influence of various physicochemical and physiological parameters on the rate of alveolar cleansing. The results obtained confirmed our hypothesis and two examples of the model verification were also shown.

Kinetics of particle retention in the human respiratory tract.

A mathematical model of retention of insoluble aerosol particles penetrating the lungs during inhalation has been described. Based on data of the streams of deposited particles and their residence times in the subsequent generations of bronchial tree the retention dynamics of particles with diameters 5, 1 and 0.01 microns in the air-spaces has been determined.

Dynamics of pulmonary surfactant system and its role in alveolar cleansing.

Qualitative descriptions of the surfactant film behaviour and the concept of hydrodynamical clearance in the alveoli are presented, and the possibilities of modelling of dynamics of this system mathematically are discussed. Using the model formulated it is shown that under dynamic conditions physiochemical surface phenomena may lead to net flow of the liquid layer (together with the dust particles) out of the alveoli. The effects of some parameters (surfactant activity and its production, viscosity of the liquid layer, size and geometry of the bronchoalveolar system, shape of respiratory curve) on the clearance rate are demonstrated. The results obtained are discussed critically.