Morton Lippmann

Deposition, retention, and clearance of inhaled particles.

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.

Health effects of ozone. A critical review

Health and pollution control professionals and the general public need to develop a more complete understanding of the health effects of ozone (O3) because: 1) we have been unable to significantly reduce ambient O3 levels using current strategies and controls; 2) in areas occupied by more than half of the U.S. population, current peak ambient O3 concentrations are sufficient to elicit measurable transient changes in lung function, respiratory symptoms, and airway inflammation in healthy people engaged in normal outdoor exercise and recreational activities; 3) the effects of O3 on transient functional changes are sometimes greatly potentiated by the presence of other environmental variables; and 4) cumulative structural damage occurs in rats and monkeys exposed repetitively to O3 at levels within currently occurring ambient peaks, and initial evidence from dosimetry models and interspecies comparisons indicate that humans are likely to be more sensitive to O3 than rats. The extent and significance of these effects, and the multibillion dollar costs of ambient O3 controls need to be considered in any future revisions of ambient standards and the Clean Air Act. The transient effects of O3 are more closely related to cumulative daily exposure than to one hour peak concentrations, and future revisions of the ambient standard for O3 should take this into account. The effects of long-term chronic exposure to O3 remain poorly defined, but recent epidemiologic and animal inhalation studies suggest that current ambient levels are sufficient to cause premature aging of the lungs. More research is needed to determine the need for a standard with a seasonal or annual average concentration limit.

Associations between ozone and daily mortality: analysis and meta-analysis.

Background: There is ample evidence that short-term ozone exposure is associated with transient decrements in lung functions and increased respiratory symptoms, but the short-term mortality effect of such exposures has not been established. Methods: We conducted a review and meta-analysis of short-term ozone mortality studies, identified unresolved issues, and conducted an additional time-series analysis for 7 U.S. cities (Chicago, Detroit, Houston, Minneapolis–St. Paul, New York City, Philadelphia, and St. Louis). Results: Our review found a combined estimate of 0.39% (95% confidence interval = 0.26–0.51%) per 10-ppb increase in 1-hour daily maximum ozone for the all-age nonaccidental cause/single pollutant model (43 studies). Adjusting for the funnel plot asymmetry resulted in a slightly reduced estimate (0.35%; 0.23–0.47%). In a subset for which particulate matter (PM) data were available (15 studies), the corresponding estimates were 0.40% (0.27–0.53%) for ozone alone and 0.37% (0.20–0.54%) with PM in model. The estimates for warm seasons were generally larger than those for cold seasons. Our additional time-series analysis found that including PM in the model did not substantially reduce the ozone risk estimates. However, the difference in the weather adjustment model could result in a 2-fold difference in risk estimates (eg, 0.24% to 0.49% in multicity combined estimates across alternative weather models for the ozone-only all-year case). Conclusions: Overall, the results suggest short-term associations between ozone and daily mortality in the majority of the cities, although the estimates appear to be heterogeneous across cities.

Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans

Regional deposition of inhaled particles was studied experimentally in a hollow cast of the human larynx-tracheobronchial tree extending through the first six branching levels, and in twenty-six non-smoker human volunteers in vivo. Results of the hollow cast study indicated a linear dependence of particle deposition efficiency on the Stokes number for aerosols with aerodynamic diameters greater than 2 micrometers. Alveolar and total respiratory tract in vitro deposition in healthy non-smokers was minimal for particles of approximately 0.4 micrometers, and alveolar deposition for mouthpieces inhalations peaked for particles of approximately 3 micrometers. A new anatomic parameter, the bronchial deposition size (BDS), is introduced to permit the classification of various individuals and populations according to their tracheobronchial deposition efficiencies. The average BDSs were 1.20 cm for 26 healthy non-smokers, 1.02 cm for 46 cigarette smokers, 0.90 cm for 19 clinical patients being treated for obstructive lung disease and 0.60 cm for six severely disabled patients.

The Effect of Particle Size on the Regional Deposition of Inhaled Aerosols in the Human Respiratory Tract

Abstract The effect of particle size on the regional deposition of aerosols inhaled through the mouth was determined in 93 studies on 34 subjects. The test aerosols were spherical monodisperse insoluble iron oxide particles (specific gravity 2.5) containing radioactive tags, ranging in median unit density diameter from 2.1 to 12.5-microns (σ ≅ 1.08). Particles deposited on the bronchial tree were translocated to the stomach by mucociliary clearance which was essentially complete within the first day. The proportion of the initial lung burden of radioactive particles removed during the first 24 hours provided a functional measure of tracheo-bronchial deposition. A portion of the inhaled aerosol was deposited in the head by impaction. As an impactor, the tracheobronchial tree is more efficient. For each individual subject, head and tracheobronchial deposition increased with increasing particle size. Alveolar depositions decreased with size for particles larger than 4-microns.

Cardiovascular effects of nickel in ambient air.

Background Fine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations. Objective Our objective in this study was to determine the most influential FPM components. Methods A mouse model of atherosclerosis (ApoE−/−) was exposed to either filtered air or concentrated FPM (CAPs) in Tuxedo, New York (85 μg/m3 average, 6 hr/day, 5 days/week, for 6 months), and the FPM elemental composition was determined for each day. We also examined associations between PM components and mortality for two population studies: National Mortality and Morbidity Air Pollution Study (NMMAPS) and Hong Kong. Results For the CAPs-exposed mice, the average of nickel was 43 ng/m3, but on 14 days, there were Ni peaks at ~ 175 ng/m3 and unusually low FPM and vanadium. For those days, back-trajectory analyses identified a remote Ni point source. Electrocardiographic measurements on CAPs-exposed and sham-exposed mice showed Ni to be significantly associated with acute changes in heart rate and its variability. In NMMAPS, daily mortality rates in the 60 cities with recent speciation data were significantly associated with average Ni and V, but not with other measured species. Also, the Hong Kong sulfur intervention produced sharp drops in sulfur dioxide, Ni, and V, but not other components, corresponding to the intervention-related reduction in cardiovascular and pulmonary mortality. Conclusions Known biological mechanisms cannot account for the significant associations between Ni with the acute cardiac function changes in the mice or with cardiovascular mortality in people at low ambient air concentrations; therefore, further research is needed.

Effects of Metals within Ambient Air Particulate Matter (PM) on Human Health

We review literature providing insights on health-related effects caused by inhalation of ambient air particulate matter (PM) containing metals, emphasizing effects associated with in vivo exposures at or near contemporary atmospheric concentrations. Inhalation of much higher concentrations, and high-level exposures via intratracheal (IT) instillation that inform mechanistic processes, are also reviewed. The most informative studies of effects at realistic exposure levels, in terms of identifying influential individual PM components or source-related mixtures, have been based on (1) human and laboratory animal exposures to concentrated ambient particles (CAPs), and (2) human population studies for which both health-related effects were observed and PM composition data were available for multipollutant regression analyses or source apportionment. Such studies have implicated residual oil fly ash (ROFA) as the most toxic source-related mixture, and Ni and V, which are characteristic tracers of ROFA, as particularly influential components in terms of acute cardiac function changes and excess short-term mortality. There is evidence that other metals within ambient air PM, such as Pb and Zn, also affect human health. Most evidence now available is based on the use of ambient air PM components concentration data, rather than actual exposures, to determine significant associations and/or effects coefficients. Therefore, considerable uncertainties about causality are associated with exposure misclassification and measurement errors. As more PM speciation data and more refined modeling techniques become available, and as more CAPs studies involving PM component analyses are performed, the roles of specific metals and other components within PM will become clearer.

Associations between Health Effects and Particulate Matter and Black Carbon in Subjects with Respiratory Disease

We measured fractional exhaled nitric oxide (FENO), spirometry, blood pressure, oxygen saturation of the blood (SaO2), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter ≤10 μm or ≤2.5 μm, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects’ homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 μg/m3 increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9–8.9] and 4.2 ppb (95% CI, 1.3–7.1) increase in FENO, respectively. A 1 μg/m3 increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FENO of 2.3 ppb (95% CI, 1.1–3.6), 4.0 ppb (95% CI, 2.0–5.9), and 1.2 ppb (95% CI, 0.2–2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO2 in these subjects. Results from this study indicate that FENO may be a more sensitive marker of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.

Acute respiratory health effects of air pollution on children with asthma in US inner cities

BACKGROUND Children with asthma in inner-city communities may be particularly vulnerable to adverse effects of air pollution because of their airways disease and exposure to relatively high levels of motor vehicle emissions. OBJECTIVE To investigate the association between fluctuations in outdoor air pollution and asthma morbidity among inner-city children with asthma. METHODS We analyzed data from 861 children with persistent asthma in 7 US urban communities who performed 2-week periods of twice-daily pulmonary function testing every 6 months for 2 years. Asthma symptom data were collected every 2 months. Daily pollution measurements were obtained from the Aerometric Information Retrieval System. The relationship of lung function and symptoms to fluctuations in pollutant concentrations was examined by using mixed models. RESULTS Almost all pollutant concentrations measured were below the National Ambient Air Quality Standards. In single-pollutant models, higher 5-day average concentrations of NO2, sulfur dioxide, and particles smaller than 2.5 microm were associated with significantly lower pulmonary function. Higher pollutant levels were independently associated with reduced lung function in a 3-pollutant model. Higher concentrations of NO2 and particles smaller than 2.5 microm were associated with asthma-related missed school days, and higher NO2 concentrations were associated with asthma symptoms. CONCLUSION Among inner-city children with asthma, short-term increases in air pollutant concentrations below the National Ambient Air Quality Standards were associated with adverse respiratory health effects. The associations with NO2 suggest that motor vehicle emissions may be causing excess morbidity in this population.

Asbestos exposure indices

The ability of inhaled asbestos to produce asbestosis, lung cancer, and mesothelioma in both humans and animals is well established, and asbestos exposures in the occupational and general community environment are recognized as significant hazards. However, it has not been possible to establish realistic and credible dose-response relationships, primarily because of our inability to define which constituents of the aerosols produce or initiate the pathological responses. It is generally acknowledged that the responses are associated with the fibers rather than the nonfibrous silicate mineral of the same chemical composition. Available data from experimental studies in animals exposed by injection and inhalation to fibers of defined size distributions are reviewed, alone with data from studies of fiber distributions in lungs of exposed humans in relation to the effects associated with the retained fibers. It is concluded that asbestosis is most closely related to the surface area of retained fibers, that mesothelioma is most closely associated with numbers of fibers longer than approximately 5 microns and thinner than approximately 0.1 micron, and that lung cancer is most closely associated with fibers longer than approximately 10 microns and thicker than approximately 0.15 micron. The implications of these conclusions on methods for fiber sampling and analyses are discussed.