Ultrafine particle deposition and clearance in the healthy and obstructed lung

Numerous epidemiologic studies have shown associations between exposure to particulate air pollution and acute increases in morbidity and mortality, particularly in persons with chronic obstructive pulmonary disease. The dosimetry of ultrafine particles in the human lung is poorly characterized. We studied the deposition and clearance of an ultrafine technetium-99m-labeled aerosol in 10 patients with chronic obstructive pulmonary disease and in 9 healthy subjects. Particle retention was followed for 2 hours after inhalation and again at 24 hours by γ scintigraphy. Central-to-peripheral ratios indexed airway deposition. Particle accumulation in the liver was examined by quantifying activity below the right lung. The dose rate for an aerosol exposure of 10 μg/m3 was calculated. Patients had a significantly greater dose rate than healthy subjects (2.9 ± 1.0 versus 1.9 ± 0.4 μg/h, p = 0.02). Central-to-peripheral ratios were slightly greater in patients than in healthy subjects (1.11 ± 0.10 versus 1.01 ± 0.11, p = 0.05). Clearance did not statistically differ between health and disease. On average, 24-hour retention was 85 ± 8% (corrected for isotope dissolution). No accumulation in the liver's vicinity was observed. Data suggest that relative to healthy subjects, patients with moderate-to-severe airways obstruction receive an increased dose from ultrafine particle exposure

Filtration Efficiency of Hospital Face Mask Alternatives Available for Use during the COVID-19 Pandemic

Importance: Procuring respiratory protection for clinicians and other health care workers has become a major challenge of the coronavirus disease 2019 (COVID-19) pandemic and has resulted in nonstandard practices such as the use of expired respirators and various decontamination processes to prolong the useful life of respirators in health care settings. In addition, imported, non-National Institute for Occupational Safety and Health (NIOSH)-approved respirators have been donated or acquired by hospitals as a potential replacement for limited NIOSH-approved N95 respirators. Objective: To assess fitted filtration efficiencies (FFEs) for face mask alternatives used during the COVID-19 pandemic. Design, Setting, and Participants: For this quality-improvement study conducted between April and June 2020, we used the Occupational Safety and Health Administration's Quantitative Fit Testing Protocol for Filtering Facepiece Respirators in a laboratory atmosphere supplemented with sodium chloride particles to assess the FFEs of a variety of respirators worn by a male volunteer and female volunteer. Main Outcomes and Measures: The FFEs of respirators commonly worn by clinicians and other health care workers and available respirator alternatives during the COVID-19 pandemic. Results: Of the 29 different fitted face mask alternatives tested on 1 man and 1 woman, expired N95 respirators with intact elastic straps and respirators subjected to ethylene oxide and hydrogen peroxide sterilization had unchanged FFE (>95%). The performance of N95 respirators in the wrong size had slightly decreased performance (90%-95% FFE). All of the respirators not listed as approved in this evaluation (n = 6) failed to achieve 95% FFE. Neither of the 2 imported respirators authorized for use by the Centers for Disease Control and Prevention that were not NIOSH-approved tested in this study achieved 95% FFE, and the more effective of the 2 functioned at approximately 80% FFE. Surgical and procedural face masks had filtering performance that was lower relative to that of N95 respirators (98.5% overall FFE), with procedural face masks secured with elastic ear loops showing the lowest efficiency (38.1% overall FFE). Conclusions and Relevance: This quality-improvement study evaluating 29 face mask alternatives for use by clinicians interacting with patients during the COVID-19 pandemic found that expired N95 respirators and sterilized, used N95 respirators can be used when new N95 respirators are not available. Other alternatives may provide less effective filtration

Cask System Design Guidance for Robotic Handling

Remote automated cask handling has the potential to reduce both the occupational exposure and the time required to process a nuclear waste transport cask at a handling facility. The ongoing Advanced Handling Technologies Project (AHTP) at Sandia National Laboratories is described. AHTP was initiated to explore the use of advanced robotic systems to perform cask handling operations at handling facilities for radioactive waste, and to provide guidance to cask designers regarding the impact of robotic handling on cask design. The proof-of-concept robotic systems developed in AHTP are intended to extrapolate from currently available commercial systems to the systems that will be available by the time that a repository would be open for operation. The project investigates those cask handling operations that would be performed at a nuclear waste repository facility during cask receiving and handling. The ongoing AHTP indicates that design guidance, rather than design specification, is appropriate, since the requirements for robotic handling do not place severe restrictions on cask design but rather focus on attention to detail and design for limited dexterity. The cask system design features that facilitate robotic handling operations are discussed, and results obtained from AHTP design and operation experience are summarized. The application of these design considerations is illustrated by discussion of the robot systems and their operation on cask feature mock-ups used in the AHTP project. 11 refs., 11 figs

Mucociliary clearance as an outcome measure for cystic fibrosis clinical research

Current concepts of cystic fibrosis (CF) pathophysiology link ion transport abnormalities to reduced airway surface liquid (ASL) hydration and impaired mucus clearance. It is likely that correction of the defects that cause ASL dehydration will prevent degradation of mucus clearance, thereby preventing the initiation and/or progression of CF lung disease. A number of novel therapeutic agents aimed at the earliest steps in disease pathogenesis are now under development for the treatment of CF lung disease. Consequently, there is a tremendous need to develop methods that directly assess the effects of these agents on the underlying pathophysiologic process in the target organ. The measurement of mucociliary clearance (MCC) is a highly biologically relevant outcome, but one that is in need of further development. Here, we describe important methodologic aspects of MCC measurement and issues that have limited its use as an outcome measure in the past. Furthermore, we outline the steps that are being carried out now, and will be carried out in the future, to improve the performance of these studies in clinical trials. A systematic approach to optimizing and standardizing the measurement of MCC should greatly advance our ability to assess novel therapies at a relatively early stage of drug development. The resulting data may then be used to select those candidates that should be rapidly advanced into larger clinical trials

Nonmonotonic dependence of the absolute entropy on temperature in supercooled Stillinger-Weber silicon

Using a recently developed thermodynamic integration method, we compute the precise values of the excess Gibbs free energy (G^e) of the high density liquid (HDL) phase with respect to the crystalline phase at different temperatures (T) in the supercooled region of the Stillinger-Weber (SW) silicon [F. H. Stillinger and T. A. Weber, Phys. Rev. B. 32, 5262 (1985)]. Based on the slope of G^e with respect to T, we find that the absolute entropy of the HDL phase increases as its enthalpy changes from the equilibrium value at T \ge 1065 K to the value corresponding to a non-equilibrium state at 1060 K. We find that the volume distribution in the equilibrium HDL phases become progressively broader as the temperature is reduced to 1060 K, exhibiting van-der-Waals (VDW) loop in the pressure-volume curves. Our results provides insight into the thermodynamic cause of the transition from the HDL phase to the low density phases in SW silicon, observed in earlier studies near 1060 K at zero pressure.Comment: This version is accepted for publication in Journal of Statistical Physics (11 figures, 1 table

Assessing the effect of beard hair lengths on face masks used as personal protective equipment during the COVID-19 pandemic

Background Globally, a large percentage of men keep a beard at least occasionally. Workplace regulations prohibit beards with N95 respirators, but there is little information on the effect of beards with face masks worn by the public for protection against SARS-CoV-2. Methods and findings We examined the fitted filtration efficiency (FFE) of five commonly worn protective face masks as a function of beard length following the US Occupational Safety and Health Administration Quantitative Fit Test: N95 (respirator), KF94 and KN95, surgical/procedure, and cloth masks. A comparison using N95 respirators was carried out in shaven and bearded men. A detailed examination was conducted for beard lengths between 0 and 10 mm (0.5 mm increments). The effect of an exercise band covering the beard on FFE was also tested. Although N95 respirators showed considerable variability among bearded men, they had the highest FFE for beard lengths up to 10 mm. KF94 and KN95 masks lost up to 40% of their FFE. Procedure and cotton masks had poor performance even on bare skin (10–30% FFE) that did not change appreciably with beard length. Marked performance improvements were observed with an exercise band worn over the beard. Conclusions Though variable, N95 respirators offer the best respiratory protection for bearded men. While KF94 and KN95 FFE is compromised considerably by increasing beard length, they proved better options than procedure and cotton face masks. A simple exercise band improves FFE for face masks commonly used by bearded men during the COVID-19 pandemic

Retention and intracellular distribution of instilled iron oxide particles in human alveolar macrophages

Bronchoalveolar lavage (BAL) was used to sample retention of particles within the alveolar macrophage (AM) compartment at various times from 1 to 91 d following intrapulmonary instillation of 2.6-μm-diameter iron oxide (Fe2O3) particles in human subjects. Particles were cleared from the lavagable AM compartment in a biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term clearance half-time of 110 d, comparable to retention kinetics determined by more traditional methods. The intracellular distribution of particles within lavaged AMs was similar in bronchial and alveolar BAL fractions. AMs with high intracellular particle burdens disappeared from the lavagable phagocytic AM population disproportionately more rapidly (shorter clearance half-time) than did AMs with lower particle burdens, consistent with the occurrence of a particle redistribution phenomenon as previously described in similar studies in rats. The rates of AM disappearance from the various particle burden categories was generally slightly slower in bronchial fractions than in alveolar fractions. The instillation of particles induced a transient acute inflammatory response at 24 h postinstillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages in BAL fluids. This response was subclinical and was resolved within 4 d PI

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung during Tidal Breathing

Background: To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar gamma scintigraphy in seven subjects. Methods: Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar gamma scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 μm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data - apices aligned - using a transmission scan as reference. The ratio of fractional alveolar deposition to fractional ventilation of each quartile (r) was used to evaluate ventilation and deposition matching (r > 1, regional aerosol deposition fraction larger than regional ventilation fraction). Results: r was not significantly different from 1 for all regions (1.04 ± 0.25, 1.08 ± 0.22, 1.03 ± 0.17, 0.92 ± 0.13, apex to diaphragm, p > 0.40) at the alveolar level (r22h). For retention times r0h and r1h30, only the diaphragmatic region at r1h30 differed significantly from 1. Conclusions: These results support the hypothesis that alveolar deposition is directly proportional to ventilation for ∼5 μm particles that are inhaled in the supine posture and are consistent with previous simulation predictions that show that convective flow is the main determinant of aerosol transport to the lung periphery

Radiolabeling an Electronic Cigarette Aerosol Using Technetium Carbon Ultrafine Particles

Background: Electronic cigarettes (ECIGs) are widely used, but their health effects are not well known. ECIG exposure is difficult to quantify, and a direct measurement of deposition would be beneficial to in vivo and in vitro toxicity studies. The aim of this study was to demonstrate effective radiolabeling of an ECIG. Methods: A technetium-99m-labeled carbon ultrafine (TCU) aerosol was generated and introduced to a fourth-generation ECIG before nucleation and aerosol formation. The aerosolized e-liquid was a commercially available strawberry flavor containing 1.2% nicotine in a 55% propylene glycol and 45% vegetable glycerine base. An ECIG power setting of 100 W was selected. Mass and radioactivity were measured on each stage within a Sierra Cascade Impactor at 14 L/min to verify the labeling technique using the calculated aerodynamic diameters. A strong positive correlation (R 2 > 0.95) between the percent activity and percent mass deposition on each stage provides a reliable validation of colocation. Results: Unlabeled ECIG aerosol from the chosen e-liquid produced a mass median aerodynamic diameter (MMAD) of 0.85 μm. An ECIG labeled with TCU produced an aerosol with an activity median aerodynamic diameter of 0.84 μm and an MMAD of 0.84 μm. The relative mass versus radioactivity on each plate was highly correlated (average R 2 = 0.973, p < 0.001). Conclusion: A TCU radiolabel was generated and shown to associate with the mass of an aerosol produced by a typical commercially available ECIG. Thus, the radioactivity of the deposited aerosol may be used to determine ECIG aerosol deposition for the future in vivo and in vitro dosimetry studies of the third- and fourth-generation ECIGs

Induced sputum derives from the central airways: Confirmation using a radiolabeled aerosol bolus delivery technique

Indirect evidence suggests that induced sputum derives from the surfaces of the bronchial airways. To confirm this experimentally, we employed a radiolabeled aerosol bolus delivery technique that preferentially deposits aerosol in the central airways in humans. We hypothesized that there would be significantly more radioactivity recovered in an induced sputum sample, and greater airways clearance of radiolabeled particles, immediately after a central versus peripheral airways deposition. Ten healthy volunteers underwent radiolabeled aerosol deposition (99mTc sulfur colloid particles) to the central and peripheral airways on separate occasions followed immediately by induced sputum or no sputum (control), while seated in front of a gamma camera. Radioactivity was measured in the selected sputum sample, processed cell pellet, and supernatant fraction. Significantly more radioactivity was present in all portions of the sputum sample after central versus peripheral airways deposition (i.e., selected sample: 15,607 counts ± 2,985 versus 943 counts ± 298, p = 0.001). Clearance from the whole lung was significantly greater 40 min after central versus peripheral airways deposition (48 ± 3% versus 5 ± 1%, p = 0.0001). Compared with control, induced sputum greatly enhanced clearance after central deposition (48 ± 3% versus 11 ± 6%, p = 0.0001), but not after peripheral deposition (5 ± 1% versus 3 ± 0.8%). These results provide direct evidence that induced sputum derives from the central airways with little or no contribution from the peripheral airways