1
ENVR732-001 Fall 2009
Health effects of outdoor and indoor air pollution.
An integrated interdisciplinary approach.
ENVR 732, section 1.
Dept. of Environmental Sciences and Engineering, School of Public Health, and
Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine
1. Class time: Fall semester, every Tue and Thu 9:30 - 10:45.
2. Classroom: McGavran-Greenberg #2304
3. Description
No prerequisites. However, some knowledge of basic human physiology and biochemistry will greatly facilitate comprehension of the presented material. The course is a series of lectures on health effects of ambient criteria air pollutants (ozone, NOx, SOx, CO, particulates, lead) and selected indoor air pollutants with emphasis on the cardiorespiratory system. The students will gain an overall understanding of the health consequences of exposures to typical pollutant atmospheres as assessed by laboratory, field and epidemiological studies. Three credit hours. Fall semester.
The course was developed to introduce you to such an important topic and area of public concern as the adverse health effects due to ambient and indoor air pollutants. It will help you to understand the basics of health problems associated with exposures to ambient, particularly "criteria" (regulated by EPA) air pollutants. To comprehend the interaction as well as interdependence of processes involved in identification and assessment of health hazards of environmental pollutants, the course material has integrated contributions of many disciplines, including physiology, cellular and molecular biology, immunology, genetics, dosimetry, etc. This approach should give you a good understanding of the health effects of air pollutants on normal and diseased human populations, including children. Furthermore, it will provide you with a solid framework for detailed studies of more specific areas of interest offered by the existing course program.
4. Instructor
M. Hazucha, M.D., Ph.D., Center for Environmental Medicine, Asthma and Lung Biology (CEMALB), and Dept. of Medicine (Pulmonary), UNC
966-0770,
mail:Center for Environmental Medicine, Asthma and Lung Biology,
Univ. of North Carolina, CB #7310
Chapel Hill, NC27599-7310.
5. Faculty:
N. Alexis, Ph.D., CEMALB, and Dept. of Pediatrics,
966-9915,
W. Bennett, Ph.D., CEMALB and Dept. of Medicine (Pulmonary), UNC
966-6229,
P. Bromberg, M.D.,CEMALB and Dept. of Medicine (Pulmonary), UNC,
966-0774,
J. Carson, Ph.D., CEMALB, and Dept. of Pediatrics, UNC, and Dept. of Anatomy and Cell Biology, 966-0763,
W. Cascio, M.D., Chief, Division of Cardiology, BrodySchool of Medicine at ECU,
252-744-0083,
D. Diaz-Sanchez, M.D., Chief, CRB, NHEERL, US EPA,
966-0676,
I. Gilmour, Ph.D., NHEERL, US EPA
966-0663,
I. Jaspers, Ph.D., CEMALB, UNC,
966-8657,
S.Kleeberger,Ph.D., Director, Environmental Genetics Group, NIH, NIEHS,
541-3540,
M. Madden, Ph.D., NHEERL, US EPA and Dept. Environ. Sci. Eng., UNC
966-6257,
L. Neas, Ph.D., NHEERL, US EPA
966-9961,
D. Otto, Ph.D., NHEERL, US EPA
966-6226,
D. Peden, M.D., Director, CEMALB, Dept. of Pediatrics (Pulmonary/Allergy), UNC,
966-0768,
J. Rogers, Ph.D., Chief, Developmental Biology Branch, NHEERL, US EPA, MD-67
541-5177,
J. Rosati, Ph.D.,NHSRC, US EPA
541-9429,
G. Shoaf, Ph.D., NCEA, US EPA, B243-01
541-4155,
K. Yeatts, CEMALB, UNC,
843-1841,
Should any student wish to discuss the presented and related material of the course, please contact the respective faculty member and make an appointment.
6. Grading: The final grade (average of three exams) for this course follows The Gradual School Handbook grade scale (p. 7). However, each exam question will be graded according to a percentage scale below. The grades will be normalized by the instructor. The following criteria will be used by the faculty as a guideline to grading essay questions.
95-100%(H) Clear mastery of the question; precise and concise organization; depth and scope of discussion ideally suited to the question; if applicable, some evidence of creative insight and an ability to deal with controversies and reservations.
80-94% (P)Facts are accurate; evidence of reasonable depth of knowledge; evidence that the major issues involved are clearly understood; well-organized; answer contains a judicious selection of available facts.
60-79% (L)A few factual errors; major issues are covered but not in depth; good but not outstanding organization; barely satisfactory.
50-59%(F)Several factual errors; superficial coverage of the area; coherent but weak organization; although the answer is partially correct, it lacks accuracy and completeness.
31-49% (F)Evidence of major gaps in the area; organization so poor that the answer may be difficult to follow; clear evidence of misunderstanding of major issues.
0-30%(F)Either doesn't answer the question, or clearly demonstrates no understanding of the issue.
7.Reference texts and books (at the reserve desk in the Health Sciences Library):
There is no required textbook, but if you can afford it get the book by Holgate et al. Air Pollution and Health, 1999. Most of the lectures material comes from this book. The course required reading material consists of selected references and, for some lectures, handouts to be distributed before a lecture. The required references can accessed through HSL Electronic Reserves. The password will be given to you during the first lecture. Additional suggested reading material (reviews, chapters, and articles) has been selected from books and journals available in the HSL. For those who wish to expand their knowledge of a topic selected books listed below are on reserve for this course in the HSL as well.
Books/Reports:
1. Holgate,S.T., Koren,H.S., Samet, J.M., and Maynard,R.L., eds., Air Pollution and Health. London, UK: Academic Press, 1999. WA754 A29795 1999
2. W. M. Foster, D. L. Costa, eds. Air pollutants and the respiratory tract. Boca Raton : Taylor & Francis/CRC Press, 2005. WF 140 A2978 2005
3. Jane Q. Koenig. Health effects of ambient air pollution : how safe is the air we breathe? Boston : Kluwer Academic, 2000. WA 754 K78h 2000
4 M. D. Cohen, J. T. Zelikoff, R. B. Schlesinger,eds. Pulmonary immunotoxicology . Boston : Kluwer Academic Publishers, 2000. WF 600 P98349 2000
5. Levitzky, M. G. Pulmonary Physiology. New York: McGrawHill, Inc. Health Professionals Division, 1999, p. 1299. WF600 L666p 1999
6. Amdur, M.O., Doull, J., Klaassen C.D., eds. Casarett and Doull's Toxicology. The Basic Science of Poisons. New York: McGrawHill, Inc., 1996, p. 11033. QV600 C335 1996
7. Lipfert, F.W. Air Pollution and Community Health. New York: Van Nostrand Reinhold, 1994, p. 1-556. WA754 L764a 1994
8. M. Lippmann.Environmental toxicants : human exposures and their health effects / Edition 2nd ed. New York : Wiley-Interscience, 2000. WA 671 E6105 2000
9. D. E.Gardner, J. Crapo, R. O. McClellan , eds.Toxicology of the Lung. New York: Raven Press, 1999, p.1-672. WF600 T755 1999
10.Air Quality Criteria for Ozone and Related Photochemical Oxidants. US EPA, EPA/600/R-05/004a-c /, Vol. III, 2006.
11. EPA document. Air quality criteria for carbon monoxide.EPA 1.23/6:600/P-99/001 F
12. Ayers, J, Maynard R, Richards, R., eds.,Air Pollution and Health. London, UK: ImperialCollege Press, 1999. WA754 A29794 2006
13. P. Brimblecombe, R. L. Maynard, eds. The urban atmosphere and its effects London ; River Edge, NJ : Imperial College Press, 2001. WA 754 U722 2001
14. P. Witorsch, S. V. Spagnolo, eds, Air pollution and lung disease in adults. Boca Raton, Fla. : CRC Press, 1994. WF 600 A2975 1994
15. M. Krzyzanowski, B. Kuna-Dibbert and J.Schneider, eds.,Health effects of transport-related air pollution.Copenhagen : World Health Organization Europe, 2005. WA 754 H4343 2005
16. D.L. Dungworth .et al. eds., Relationships between respiratory disease and exposure to air pollution.Washington : ILSI Press, 1998. WA 754 R382 1998
17. D. G. Penney, ed., Carbon monoxide toxicity,Boca Raton ; CRC Press, 2000.
QV 662 C2647 2000
Class calendar:
Aug.25---Introduction: Course objectives, structure, exams, readings;
History of air pollution and health. M.J.Hazucha...... 7
Aug.27--- Anatomy and physiology of the human respiratory tract: aspects relevant to systemic and respiratory effects of air pollution.P.A.Bromberg 9
Sept.1---Methods in assessment of sensory and organ effects, and pulmonary function changes induced by air pollutants. M. J. Hazucha 10
Sept.3---Biological markers. Interdisciplinary methodologies for assessment of adverse health effects. M. Madden 11
Sept.8---Cellular responses and mechanisms of pollutant-induced effects. I. Jaspers...... 12
Sept. 10---Dosimetry of inhaled gases and particulates. W. Bennett...... 13
Sept. 15---Health effects of particulate matter: laboratory studies. W. Bennett...... 14
Sept. 17---Epidemiology in assessment of health effects of air pollutants. K. Yeatts ...... 15
Sept. 22---Gene-air pollutants-health interaction. S. Kleeberger...... 17
Sept. 24---Immuno-toxicological effects of air pollutants. M. I. Gilmour...... 18
Sept.29---Animal toxicology. Interspecies comparison and extrapolation of the effects of air pollutants to man. M. I. Gilmour 19
TAKE HOME EXAM
Oct.1---Controlled human exposure studies in assessment of health effects of ir pollutants. N Alexis...20
Oct.6---Mucociliary function and mechanisms of cellular damage and repair in the respiratory airways.. J.Carson 22
Oct.8---Diesel exhaust and organic compounds health effects. I.Jaspers...... 24
Oct. 13---Health Effects of Airborne Particulate Matter: Epidemiology Studies. L. Neas...... 25
Oct.15---Adverse health effects of indoor air (biological aerosols, home environment).J. Rosati...... 26
Oct.20---Acute effects of ozone; laboratory studies. Biochemical and immunotoxic effects. N. Alexis...27
Oct. 22...... Fall recess
Oct.27---Acute effects of ozone; laboratory studies. Systemic and lung function effects. M.J.Hazucha...28
Oct.29---Sulfur dioxide and its products: Effects on sensitive individuals. P.A.Bromberg...... 29
Nov.3---Health effects of nitrogen oxides. M.J.Hazucha...... 31
TAKE HOME EXAM
Nov. 5--- Kinetics, mechanisms of action and health effects of exposure to CO. M.J.Hazucha...... 32
Nov. 10---Health impacts of secondhand smoke. D. Diaz-Sanchez...... 33
Nov. 12---Systemic poisons; Lead and other metals. D. Otto...... 34
Nov. 17--- Health effects of pollutants mixtures. P.A. Bromberg...... 35
Nov.19---Cardiovascular effects of air pollutants. W. Cascio...... 37
Nov.24---Asthma and allergic disease. D. Peden...... 38
Nov. 26...... Thanksgiving recess
Dec.1---Approaches and challenges in health risk assessment. C. Shoaf...... 39
Dec.3---Protection of susceptible population. P.A. Bromberg...... 40
Dec.8---Developmental and reproductive toxicology. J. Rogers...... 41
FINAL TAKE HOME EXAM
Aug. 25---Introduction: Course objectives, structure, exams, readings;
History of air pollution and health. M.J.Hazucha
I.Introduction:
A.Course objective
B.Structure of the course
C.Exams
II.History, standards and trends:
A.Definition
Air pollution means the presence in the outdoor atmosphere of one or more contaminants, such as dust, fumes, gas, mist, odor, smoke, or vapor in quantities, of characteristics, and duration, such as to be injurious to human, plant, or animal life or to property, or which unreasonably interferes with the comfortable enjoyment of life and property (The Engineer=s Joint Council).
B.Significant dates in the history of air pollution
1280Henry III asks London city official to Ainquire about lime kilns using seacoal@ 20th May 1285
1300Coal for manufacturing hauled to London from Newcastle (~300 miles, county of Durham).
1306EDWARD I prohibits use of coal during a session of Parliament (died in 1307). Followed by Edward II, Richard III.
1418HENRY V establishes Commision of Inquiry to Ainquire of all such who burn coal in the city.....and to punish them with great fines and ransoms, 2nd offence to demolish their furnaces@.
1556G. AGRICOLA=s 12 volumes ADe Re Metallica@ published. ANew age@ , renaissance of arts and revival of learning (Copernicus, Leonardo da Vinci, Vesalius, Paracelsus). Work translated by Herbert Hoover, the president.
17th century Sweden. Legislation forbidding Aslash and burn land clearing@. Those who broke the law were banished to the New World.
1661J. EVELYN=s pamphlet AFumifugium@ publ. by royal command of Charles II. J.E. was founder of the Royal Society.
1713B. RAMAZZINI=s book ADe Morbis Artificum@ (43 chapters) is published
18191st English Select Committee of the British Parliament established to study and report upon smoke abatement.
18432nd English Select Committee established
1845Parliament passed the law requiring locomotives to consume their own smoke.
1863Alkali Act established industrial smoke inspectors in Britain
18661st paper on effects on health due to air pollution by W.Farr
1875Cattle death at London show due to air pollution
1881(USA)Local smoke ordinances passed in Chicago and Cincinnati declaring the emissions of smoke to be a public nuisance. Required that Afurnaces consume the smoke produced or employ devices that would do so.@ Principal fuel was coal. County-wide legislation to control AP in 1920, state-wide 1960, federal 1963.
1891(USA)Society for Prevention of Smoke established in Chicago (predecessor of APCA) published model smoke abatement ordinances to help communities in drafting legislation.
C.Significant events
1930MEUSE VALLEY, Belgium (Dec. 1-5). 63 excess death, 6000 ill. Est. 0.1-10 ppm SO2, zinc, PM, but most likely fluorides.
193715-month mobile survey of SO2 levels in 5 cities
19431st severe smog in LOS ANGELES (July 26)
1947California establishes first state regulation
1948DONORA, PA, disaster (Oct.27- Nov. 1) 20 fatalities; 2 days-60 sick, next 2 days-750, last day 1600 (total 5910). 10-week avg. 0.12 ppm SO2, 740 μg/m3 PM, 85 μg/m3 zinc. TSP max was 6000 μg/m3. Strong contribution by fluorides.
1952LONDON disaster (Dec. 5-10) 4000 excess death; 4000 μg/m3 SO2 and smoke. Mostly older individuals.
1953NEW YORK episode (Nov. 17-21). First reported in 1962. 200 excess death.
D.Clean Air Act - Britain (1956)
E.Clean Air Act - USA (1963)
Purpose
to publish and to revise from time to time a list of air pollutants
to establish Air Quality Standards (NAAQS)
#Primary standards
-set at levels which protect not only healthy but sensitive persons as well
-to be established using health protection as the sole test
#Secondary standards
-defines the components of public welfare that must be considered
-must protect against any type of adverse effect
State Implementation Plan
Dispersion Techniques
New and Modified Sources
Prevention of Deterioration
Mobile sources
F.US primary standards
U.S. National Primary Ambient Air Quality Standards
Pollutant / ppm / μg/m3 / Averaging time / StatisticsCarbon Monoxide (CO) / 9
35 / 10,000
40,000 / 8 hours
1 hour / Maximum
Maximum
Lead (Pb) / 1.5 / 3 months / Quarterly avg.
Nitrogen Dioxide (NO2) / 0.053 / 100 / Annual / Arithmetic mean
Particulate Matter (PM10)
(PM2.5) / 50
150
15
65 / Annual
24 hours
Annual
24 hours / Arithmetic mean
Maximum, multiple exceed.
99 percentile
Ozone (O3) / 0.12
0.075 / 235
157 / 1 hour
8 hours / Maximum
Sulfur Dioxide (SO2) / 0.03
0.14 / 80
365 / Annual
24 hours / Arithmetic mean
Maximum
G.Classification/categorization of air pollutants
1.For regulatory purposes
Criteria pollutants are those substances deemed to present a general risk to public heatlh and for which National Ambient Air Quality Standards (NAAQS) have been issued. Criteria pollutants are ozone, nitrogen dioxide, sulfur dioxide, lead, carbon monoxide, and particulate matter.
Hazardous air pollutants or air toxics are those substances identified with cancer, birth defects, neurotoxicity and for which ambient standards are neither appropriate nor practical. (Adapted from Lipfert, 1994).
2.By chemical properties
AClassical,@ reducing, London-type
-SOx, PM, CO
-winter months, early morning
-industrial and household fuel combustion
APhotochemical,@ oxidizing, Los Angeles-type
-ozone, HC, CO, NOx
-summer months, early afternoon
-motor vehicle fuel combustion
H.Trends in ambient air quality
Required reading:
Ross Anderson, H., Health effects of air pollution episodes, In: Air Pollution and Health, Eds. Holgate,S.T., Koren,H.S., Samet, J.M., and Maynard,R.L., Academic Press, London, UK, 1999, Ch. 21, pp. 461-482.
Aug. 27---Anatomy and physiology of the human respiratory tract: aspects relevant to systemic and respiratory effects of air pollution . P.A.Bromberg
For detailed description see Bromberg_FunctAnat.pdf at HSL reserves site
Sept. 1---Methods in assessment of sensory and organ effects,and pulmonary function changes induced by air pollutants. M. J. Hazucha
I.Subjective Symptoms
Methods for obtaining and evaluating symptoms.
II. Respiratory System
1.Static lung volumes and capacities (spirometry)
2.Lung dynamic tests (flow-volume)
3.Lung mechanics (plethysmography, airway resistance)
4.Gas exchange (diffusion, blood gases)
5.Control of ventilation (breathing pattern, exercise)
6.Bronchial Challenge Testing
III.Central Nervous System
1.ECG, evoked potentials
2.Olfaction
3.Ocular
4.Acoustic
IV. Cardiovascular System
1.Blood Pressure
2.Cardiac Output
3.Electrocardiogram
4.Peripheral Blood Flow
V.Other Organs Systems
Required reading: Handout Materials
Optional Reading:
1.Ruppel, G.L. Manual of Pulmonary Function TestingSt. Louis: Mosby, 1991
2. Cotes, J.E. Lung Function: Assessment and Application in Medicine.Oxford: Blackwell Scientific, 1993.
Sept. 3 ---Biological markers; Interdisciplinary methodologies for assessment of adverse health effects. M. Madden
I.Definition/Types of “Biomarkers”
A.Exposure
B.Effect
C.Susceptibility
II. Rationale for Study of Biomarkers and Utility of Biomarkers
III.Time course of biomarker formation
IV. Biomarkers of effects: Body Compartments of Interest:
A.Whole Lung Physiology
B.Breath
C.Nasal and Lung Lavage
D.Lung Cells & Tissue
E.Extrapulmonary Systems (Blood, Urine, Skin)
V. Susceptibility Biomarkers
Required reading:
1. Madden, M. and Gallagher, J.E. Biomarkers of exposure. In: Air Pollution and Health, Eds. Holgate,S.T., Koren,H.S., Samet, J.M., and Maynard,R.L., Academic Press, London, UK, 1999, Ch. 19, pp. 417-430
2.Henderson, R. and S.A. Belinsky. Biological markers of respiratory tract exposure. In:D.E. Gardner, J.D. Crapo, R.O. McClellan, eds. Toxicology of the Lung, second edition. Raven Press, New York. 1993. pp 253-282.
Optional Reading:
1. Papers from a symposium on biomarkers from air toxics exposure. Environ Health Persp 104, Suppl 5: 851-932, 1996.
2. La, D.K., and J.A. Swenberg. DNA adducts: biological markers of exposure and potential application to risk assessment. Mutation Res. 365:129-146. 1996.
3. Virchow, J.C. Jr., C. Kroegel, C. Walker, H. Matthys. Cellular and immunological markers of allergic and intrinsic bronchial asthma. Lung. 172:313-334. 1994.
4. Lewtas, J. Human exposure to complex mixtures of air pollutants. Toxicol. Lett. 72:163-169. 1994
5. Gonzalez, F.J., and H.V. Gelboin. Role of human cytochrome P-450s in risk assessment and susceptibility to environmentallt-based disease. J. Toxicol. Environ. Health. 40:289-308. 1993.
6. Vine, M.F. Biological markers of exposure: Current status and future research needs. Toxicol. Ind. Health 12:189-200, 1996.
Sept. 8--- Cellular responses and mechanisms of pollutant-induced effects. I. Jaspers
1.Pollutant-induced injury
i.Inflammation
ii.Inflammatory mediator production
iii.Comparison of different pollutants
2.General Signal Transduction Concepts
3.Generation of Oxidative Stress
i.Increased production of ROI
ii.Antioxidant defenses
iii.Air pollutant examples
4.Signaling Pathways Activated by Oxidant Pollutants
i.Transcription factors
1.General
2.Examples: NF-kB, AP-1, CREB
ii.Protein Kinases
1.General Classification
2.PKA
3.MAP kinases
4.Tyrosine kinases
a.Receptor Tyrosine Kinases (EGFR)
b.Non-receptor Tyrosine Kinases
iii.Arachidonic Acid Metabolism
Required Reading:
1. B. Baeza-Squiban, V. Bonvallot, S. Boland, F. Marano. Airborne Particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors. Cell Biology and Toxicology 15: 375-380, 1999
2. M.T. Krishna, A.J. Chauhan, A.J. Frew, S.T. Holgate. Toxicological Mechanisms Underlying Oxidant Pollutant-induced Airway Injury. Reviews in Environmental Health. 13: 59-71, 1998
Sept. 10---Dosimetry of inhaled gases and particulates. W. Bennett
Gases
I.Characterization of gases
solubility (e.g., SO2) and reactivity (e.g., O3)
II. Factors affecting distribution of gas uptake in the respiratory tract
breathing pattern, oral vs. nasal breathing, adsorption on particles, species
differences
III. Methods for measuring gas uptake
Particulates
I.Aerosol characterization
size distributions, concentration, hygroscopicity, surface properties
II.Mechanisms of particle deposition in the respiratory tract
impaction, sedimentation, diffusion, and interception
III.Techniques for measuring particle deposition and clearance
IV.Factors affecting total and regional pulmonary deposition
particle size, breathing pattern, airway morphology, species differences, lung disease
V.Particle clearance mechanisms
A. Mucociliary and cough clearance
B. Alveolar clearance
macrophages, dissolution, soluble vs. insoluble particles, ultrafines
VI. Factors modifying clearance kinetics
age, disease, overload, co-pollutants,
Required reading
Morgan MS and R Frank. Uptake of pollutant gases by the respiratory system. In: Respiratory Defense Mechanisms, part 1, eds JD Brain, DF Proctor, and LM Reid; New York: Marcel Dekker, 1977, pp. 157-189.