Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs.

Recently it was speculated that ultrafine particles (UFP) may translocate from deposition sites in the lungs to systemic circulation and whether long-term clearance differs between ultrafine and micrometer-sized particles. We have studied lung retention and clearance kinetics in 12 healthy male adult WKY rats up to 6 mo after an inhalation of (192)Ir-radiolabeled, insoluble, ultrafine 15- to 20-nm iridium particles. Whole-body retention was followed by external gamma counting, and particle clearance kinetics were determined by excretion radioanalysis.

Labeled carbon dioxide (C18O2): an indicator gas for phase II in expirograms.

Carbon dioxide labeled with 18O (C18O2) was used as a tracer gas for single-breath measurements in six anesthetized, mechanically ventilated beagle dogs. C18O2 is taken up quasi-instantaneously in the gas-exchanging region of the lungs but much less so in the conducting airways. Its use allows a clear separation of phase II in an expirogram even from diseased individuals and excludes the influence of alveolar concentration differences.

Lung volume is a determinant of aerosol bolus dispersion.

The technique of inhaling a small volume element labeled with particles ("aerosol bolus") can be used to assess convective gas mixing in the lung. While a bolus undergoes mixing in the lung, particles are dispersed in an increasing volume of the respired air. However, determining factors of bolus dispersion are not yet completely understood.

Sulfur-related air pollutants induce the generation of platelet-activating factor, 5-lipoxygenase- and cyclooxygenase-products in canine alveolar macrophages via activation of phospholipases A2.

Recent studies have shown that long-term in vivo exposure of dogs to neutral sulfur(IV)/sulfite aerosols induces mild inflammatory reactions, whereas the combination of neutral sulfite with acidic sulfur(VI)/sulfate aerosols evokes less pronounced effects. To understand underlying mechanisms, we studied in vitro the role of lipid mediators in the responses of alveolar macrophages (AMs) to sulfur-related compounds under neutral (pH 7) or moderate acidic (pH 6) conditions. Canine AMs incubated with sulfite at pH 7 released threefold higher amounts of platelet-activating factor than control (P < 0.

Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices.

Patients with hereditary alpha1-proteinase inhibitor (alpha1-PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, alpha1-PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled alpha1-PI (Prolastin) was studied using four different commercial inhalation devices (PARI-LC Star, HaloLite, and AKITA system in combination with LC Star and Sidestream) in six patients with alpha1-PI deficiency and mild-to-severe chronic obstructive pulmonary disease.

Can aerosol-derived airway morphometry detect early, asymptomatical lung emphysema?

The aerosol-derived airway morphometry technique (ADAM) can be used to assess non-invasively peripheral airspace dimensions. It has been shown that this technique can identify permanent peripheral airspace enlargement in patients with lung emphysema, but it is yet unknown if early stages of emphysema can be detected. In this study, 89 aluminum welders were investigated.

Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low.

Recently it was speculated that ultrafine particles may translocate from deposition sites in the lungs to systemic circulation. This could lead to accumulation and potentially adverse reactions in critical organs such as liver, heart, and even brain, consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases, as growing evidence from epidemiological studies suggests. Ultrafine (192)Ir radio-labeled iridium particles (15 and 80 nm count median diameter) generated by spark discharging were inhaled by young adult, healthy, male WKY rats ventilated for 1 h via an endotracheal tube.

Inbred strain variation in lung function.

The purpose of the present study was to determine the strain-specific phenotype variance of lung function parameters among common inbred laboratory mouse strains. In accordance with the "Mouse Phenome Project" run by The Jackson Laboratory (http://www.jax.

Ultrafine particles cause cytoskeletal dysfunctions in macrophages.

Essential cytoskeletal functions of macrophages are migration, phagocytosis of foreign materials, and intracellular transport and digestion The influence of fine and ultrafine test particles (UFP), such as TiO(2), elemental carbon, commercial carbon black, diesel exhaust particulate matter, and urban dust (UrbD), on cytoskeleton-related functions of macrophages, such as phagocytosis, phagosome transport mechanisms, and mechanical cytoskeletal integrity, were studied by flow cytometry and by cytomagnetometry. Additionally, necrosis and apoptosis caused by the test particles was detected. The diameter of the test particles ranged from 12 to 220 nm and the Brunauer-Emmet-Teller specific surface area ranged from 6 to 600 m(2)/g.

Respiratory mechanics in mice: strain and sex specific differences.

To assess the contribution of genetic background to respiratory mechanics, we developed a ventilator unit to measure lung function parameters in the mouse. We studied two commonly used inbred mice strains originating from Mus musculus domesticus (C57BL/6 and C3HeB/FeJ) and a third strain derived from Mus musculus molossinus [Japanese fancy mouse 1 (JF1)]. The ventilator allows for accurate performance of the different breathing manoeuvres required for measuring in- and expiratory reserve capacity, quasi-static and dynamic compliance, and airway resistance.

Alveolar deposition of monodisperse aerosol particles in the lung of patients with chronic obstructive pulmonary disease.

Knowledge about the regional deposition of aerosol particles is essential in order to perform efficient inhalation therapy or to minimize health risks due to environmental or occupational aerosol particles. In this study, 2 techniques were used to measure thoracic deposition and to differentiate between bronchial and alveolar deposition. The first technique was the clearance-derived regional deposition (CRD) technique and the second the single-breath regional deposition (SBRD) technique.

Increased sputum IL-8 and IL-5 in asymptomatic nonspecific airway hyperresponsiveness.

Since asymptomatic, nonspecific airway hyperresponsiveness (BHR) may be due to an enhanced local inflammatory response, we studied molecular markers of inflammation in induced sputum from subjects with asymptomatic BHR (n = 14) compared with control subjects (n = 13) and patients with chronic obstructive pulmonary disease (COPD) (n = 10). Pulmonary lung function parameters were measured by spirometry and body plethysmography. Hyperresponsiveness was defined based on histamine challenge.

Human alveolar long-term clearance of ferromagnetic iron oxide microparticles in healthy and diseased subjects.

Monodisperse ferrimagnetic microparticles (Fe3O4) with 1.3 microm geometric diameter were inhaled to study alveolar long-term clearance in healthy and diseased human subjects. Nineteen younger (age 20 to 39 years) and 20 older (age 40 to 65 years) healthy volunteers participated in the study as well as 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 15 patients with chronic obstructive bronchitis (COB).

Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages.

Agglomerates of ultrafine particles (AUFPs) may cause adverse health effects because of their large surface area. To evaluate physiologic responses of immune cells, we studied whether agglomerates of 77-nm elemental carbon [(EC); specific surface area 750 m2/g] and 21 nm titanium dioxide (TiO(2) particles (specific surface area 50 m(2)/g) affect the release of lipid mediators by alveolar macrophages (AMs). After 60-min incubation with 1 microg/mL AUFP-EC (corresponding to 7.

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis.

Impulse oscillometry in healthy nonsmokers and asymptomatic smokers: effects of bronchial challenge with methacholine.

The clinical application of respiratory impedance measurements by oscillation techniques for monitoring bronchial challenge testing is hampered by the fact that data in healthy nonsmokers and asymptomatic smokers are very limited. The objective of this study was to analyze the changes in impedance to a methacholine provocation test in healthy nonsmokers and asymptomatic smokers, and to investigate whether smokers show a different response compared to nonsmokers. The response to methacholine challenge was assessed by impulse oscillometry (IOS) (resistance R and reactance X at 5, 10, 15, 20, 25, and 35 Hz) and spirometry (FEV1, MEF50) in 105 healthy subjects (55 nonsmokers: "NS"; 50 asymptomatic smokers: "S") in whom the provocation dose of 2.

Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS.

Oxidative stress in acute respiratory distress syndrome (ARDS) is considered as an important pathophysiological mechanism in acute impairment of lung function. The present study investigated whether a pulmonary oxidant-antioxidant imbalance is indicated by substantial oxidative modification of proteins in bronchoalveolar lavage (BAL) fluid. Oxidatively modified proteins in BAL fluid, as measured by the reduction of protein carbonyl groups with tritiated borohydride, were studied in control subjects, patients with clinically established ARDS, and patients considered at-risk for ARDS because they had had coronary bypass surgery.

Total deposition of therapeutic particles during spontaneous and controlled inhalations.

Treatment of systemic diseases by means of the inhalation route is hampered by uncertainties of the drug dose applied by inhalation. In this study, the hypothesis was tested that by standardization of the breathing maneuver used for inhalation, the interindividual variability of the dose deposited intrathoracically can be reduced. Therefore, breathing pattern during routine inhalations with jet nebulizers was measured in 18 patients with lung disease.

Intrapulmonary distribution of deposited particles.

Inhalation drug delivery for both topical and systemic treatments has many advantages over oral, intravenous, or subcutaneous drug delivery. Because some drugs should be deposited within the bronchial tree and others should deposit within the respiratory zone of the lung, it should be possible to determine and influence the preferential site of drug deposition to develop efficient inhalation therapy strategies. In this article, a method that allows estimation of the longitudinal distribution of deposited particles in the lungs of individual subjects is introduced.

A Morphologic Study on the Fate of Ultrafine Silver Particles: Distribution Pattern of Phagocytized Metallic Silver in Vitro and in Vivo.

The distribution pattern of inhaled particles is an important factor for the evaluation of health effects. In this study, we morphologically investigated the fate of agglomerated ultrafine particles in macrophages in vitro and in vivo. Metallic silver (Ag) was chosen as a test particle, since it can be easily produced and detected by elemental and morphologic analyses.

Experimental analysis of flow calculations based on HRCT imaging of individual bifurcations.

Flow simulations in airways and arteries allow the non-invasive study of transport and deposition processes in these vessel systems. Individual vessel geometries as input for such simulations are highly desirable. Computed tomography (CT) permits the acquisition of binary data to reconstruct such geometries.

Noninvasive diagnosis of emphysema. Aerosol morphometry and aerosol bolus dispersion in comparison to HRCT.

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0.

Aerosol-derived airway morphometry and aerosol bolus dispersion in patients with lung fibrosis and lung emphysema.

Objective: Patients with lung emphysema show increased aerosol-derived dimensions of peripheral airspaces and increased aerosol bolus dispersion (AD). To apply these tests in epidemiologic studies, the objective of this pilot study was to investigate whether morphometric changes caused by lung fibrosis can be distinguished from those caused by emphysema.

Design: This study was designed as a cross-sectional study in which airspace dimensions and AD in patients with emphysema and in patients with fibrosis were compared.

Health effects of sulfur-related environmental air pollution. V. Lung structure.

The lungs of 8 male beagle dogs were examined morphologically and morphometrically after exposure for 13 mo to a respirable sulfur(IV) aerosol at a mass concentration of 1.53 mg m(-3) (16.5 h/day), and to an acidic sulfate aerosol carrying 15.