Motion and twisting of magnetic particles ingested by alveolar macrophages in the human lung: effect of smoking and disease

BACKGROUND: Magnetic microparticles being ingested by alveolar macrophages can be used as a monitor for intracellular phagosome motions and cytoskeletal mechanical properties. These studies can be performed in the human lung after voluntary inhalation. The influence of cigarette smoking and lung diseases on cytoskeleton dependent functions was studied. METHODS: Spherical 1.3 μm diameter ferrimagnetic iron oxide particles were inhaled by 17 healthy volunteers (40 – 65 years), 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 18 patients with chronic obstructive bronchitis (COB). The retained particles were magnetized and aligned in an external 100 mT magnetic field. All magnetized particles induce a weak magnetic field of the lung, which was detected by a sensitive SQUID (superconducting quantum interference device) sensor. Cytoskeletal reorganizations within macrophages and intracellular transport cause stochastic magnetic dipole rotations, which are reflected in a decay of the magnetic lung field, called relaxation. Directed phagosome motion was induced in a weak magnetic twisting field. The resistance of the cytoplasm to particle twisting was characterized by the viscosity and the stiffness (ratio between stress to strain) of the cytoskeleton. RESULTS: One week after particle inhalation and later macrophage motility (relaxation) and cytoskeletal stiffness was not influenced by cigarette smoking, neither in healthy subjects, nor in the patients. Patients with IPF showed in tendency a faster relaxation (p = 0.06). Particle twisting revealed a non-Newtonian viscosity with a pure viscous and a viscoelastic compartment. The viscous shear was dominant, and only 27% of the shear recoiled and reflected viscoelastic properties. In patients with IPF, the stiffness was reduced by 60% (p < 0.02). An analysis of the shear rate and stress dependence of particle twisting allows correlating the rheological compartments to cytoskeletal subunits, in which microtubules mediate the pure viscous (non-recoverable) shear and microfilaments mediate the viscoelastic (recoverable) behavior. The missing correlation between relaxation and particle twisting shows that both stochastic and directed phagosome motion reflect different cytoskeletal mechanisms. CONCLUSION: Faster relaxation and a soft cytoskeleton in patients with IPF indicate alterations in cytoskeleton dependent functions of alveolar macrophages, which may cause dysfunction's in the alveolar defense, like a slower migration, a retarded phagocytosis, a disturbed phagosome lysosome fusion and an impaired clearance

Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies

Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking

Severe Emphysema Treated by Endoscopic Bronchial Volume Reduction with Lung Sealant (AeriSeal)

Endoscopic lung volume reduction using lung sealant is a very new and innovative treatment option for patients with severe progressive and irreversible lung emphysema. A 55-year-old ex-smoker (60 pack years) referred to our center because of severe lung emphysema with progressive worsening of the obstructive ventilator pattern and clinical condition. We detected collateral channels of this patient by using the Chartis system. Therefore, we decided to treat the advanced emphysema of our patient with endoscopic volume reduction using lung sealant (AeriSeal). The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue on the lung surface in order to seal the target region to cause durable irreversible absorption atelectasis. The follow-up evaluation 12 weeks later showed improved lung function (increased FEV 1/partial oxygen pressure/peripheral oxygen saturation and a reduction of TLC and RV) with improved quality of life. Correlation between changes in primary and secondary outcome measures in the lung function parameters and 6-minute-walking test before and 12 weeks after the application of lung sealant revealed significant reduction of hyperinflation and improvement both in the flow rates and in the physical capability of this patient

Motion and twisting of magnetic particles ingested by laveolar macrophages in non-smokers and smokers: Implementation of viscoelaticity.

Ferrimagnetic iron oxide particles were inhaled by 17 healthy volunteers (9 non-smokers, 8 smokers), and the retained particles were magnetized and detected by a SQUID. Stochastic particle transport due to cytoskeletal reorganizations within macrophages (relaxation) and directed particle motion in a weak magnetic twisting field were investigated with respect to viscous and elastic properties of the cytoskeleton. Relaxation and cytoskeletal stiffness were not influenced by cigarette smoking. Relaxation and particle twisting revealed a non-Newtonian viscosity with a pure viscous and a viscoelastic compartment. Viscous and elastic data obtained from relaxation correlated with particle twisting, indicating that the proposed simple model is a reasonable approximation of cytoskeletal mechanical properties

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). In each group the subjects were divided into never smokers (NS) and active smokers (S). Clearance was measured by magnetopneumography (MPG) for 300 days after inhalation. In COB, 50% of the deposited particles were removed from the lungs after 2 days, indicating high bronchial deposits due to bronchial obstructions. In healthy NS, only 10% of the particles were removed after 2 days and cigarette smoking enhanced the fraction of fast-cleared particles. In subjects who smoked, slow clearance was significantly impaired (P &lt; . 02). Clearance half-lives (in days) for younger, healthy, NS were 124 +/- 66 (mean +/- SD) compared to 220 +/- 74 for S. Similarly for older subjects, the timeswere 162 +/- 120 for NS and 459 +/- 334 for S. The impairment of alveolar clearance due to cigarette smoking increases by 5.7 +/- 1.3 days/pack-year (P &lt; .01). Alveolar clearance was impaired in SAR and in IPF; half-lives were 275 +/- 109 days (P &lt; .05) and 756 +/- 345 days (P &lt; .02), respectively, compared to healthy NS. Most COB patients were ex-smokers, their long-term clearance was 240 +/- 74 days, which is more than healthy NS (P &lt; .01), but less than healthy S and might indicate a recovery of alveolar clearance. In view of studies using totally inert particles like Teflon, we conclude that the lung clearance measured with iron oxide tracer particles primarily reflects clearance by intraphagosomal particle dissolution within alveolar macrophages, which is impaired by cigarette smoke consumption and in patients

Fractionated exhaled breath condensate collection shows high hydrogen peroxide release in the airways.

BACKGROUND: Exhaled breath condensate (EBC) allows noninvasive monitoring of inflammation in the lung. Activation of inflammatory cells results in an increased production of reactive oxygen species, leading to the formation of hydrogen peroxide (H(2)O(2)). In addition, cigarette smoking causes an influx of inflammatory cells, and higher levels of H(2)O(2) have been found in EBC of smokers. However, there are still unresolved issues reflected by large variations in exhaled H(2)O(2) and uncertainties about the origin of H(2)O(2) release in the lung. METHODS: We collected EBC as fractionated samples from the airways and from the lung periphery in 10 nonsmokers, eight asymptomatic smokers, and in eight chronic obstructive pulmonary disease (COPD) patients, and H(2)O(2) concentration and acidity (pH) were analyzed in the airway and the alveolar fraction. RESULTS: In all subjects studied, H(2)O(2) was 2.6 times higher in the airway versus the alveolar fraction. Airway H(2)O(2) was twofold higher in smokers and fivefold higher in COPD patients compared to nonsmokers. In all study groups, there was no significant difference in deaerated pH between the airway and the alveolar sample. ONCLUSIONS: Exhaled H(2)O(2) is released at higher concentrations from the airways of all subjects studied, implying that the airways may be the dominant location of H(2)O(2) production. Because many lung diseases cause inflammation at different sites of the lung, fractionated sampling of EBC can reduce variability and maintain an anatomical allocation of the exhaled biomarkers

Pulmonary Adenocarcinoma Occurring 5 Years after Resection of a Primary Pancreatic Adenocarcinoma: A Relevant Differential Diagnosis

Ductal adenocarcinoma of the pancreas is a lethal disease. Surgical extirpation only offers the slim chance for long-term survival in localized disease. We report on a 73 year old female patient who initially underwent successful resection of pancreatic adenocarcinoma in May 2005. She was treated with adjuvant chemotherapy with gemcitabine. In October 2010 the patient noticed increasing dyspnea with haemoptysis. She was soon referred to our center. After the diagnosis of pulmonary adenocarcinoma with widespread metastasis, she was treated with systemic chemotherapy. For a period of next three years, she was treated with different chemotherapy regimens due to repeated episodes of tumor progression. To the best of our knowledge after reviewing the literature, this case represents an unusually clinical course with metachronous pulmonary adenocarcinoma arising after treatment of a primary pancreatic cancer after a long latency period