What we now know about the WTC dust
particles
Particle quantity and size
• 1.2 million tons of building
materials
• 90% particles >10 Qn diameter
• 11,000 tons of particles < 2.5
mm were released
• Gases and fumes from fires that
burned until December 19, 2001
*Lioy et al. Environmental Health Perspectives Vol 110,, July 2002
Early onset disease: Acute eosinophilic pneumonia
in a firefighter
Rom et al. Am J Respir Crit Care Med 2002
Mineralogic analysis of bronchoalveolar lavage from
firefighter
(A) Amosite asbestos fiber (uncoated)
(B) Fly ash particle
(C) Degraded fibrous glass.
305 commercial asbestos fibers/10 6 macrophages
Rom et al. Am J Respir Crit Care Med 2002
Chrysotile Asbestos
1
LUNG CANCER AND ASBESTOS EXPOSURE
• North American insulators union with 17,800 workers
followed from 1967-1987 revealed
► Lung cancer 1 166 deaths 267 expected RR 4.4
► Mesothelioma 457 deaths (9%)
1 Synergism with cigarette smoking
► Risk decreases dramatically after quitting
• Since the removal of asbestos from insulation materials
in the early 1970s, death rates have declined for lung
cancer but continued to increase for mesothelioma
AotheljPtna
PLEURAL PLAQUES AND RISK FOR BRONCHIAL
CARCINOMA AND MESOTHELIOMA
• Epidemiologic survey of 1,596 men with pleural plaques in
Uppsala, Sweden, were followed from 1963-1985.
•Bilateral lesions
•> 5MM thick and/or calcified, well-demarcated.
•No remnants of pleurisy, i.e. costophrenic angles not
obliterated.
• 50 Bronchial carcinomas observed while 32.1 expected after
correction for smoking (O/E 1.6; CI 1.2-2.1).
2.3 (CI 1.1-4.4) with asbestosis
•1.4 (CI 1.0-2.0) without asbestosis
• 9 Mesotheliomas with 0.8 expected (O/E 11.3; CI 5.1-21.4).
Hillerdal G, Chest 1994; 105:144-150.
WHO" WORKED Z MONTHS
All Cancer Lung Cancer
aJUruHd if
Eipq-M
■a is 10 n h
10 15 10 u
Elapsed Years Since Onset Of Work
American Cancer Society Follow-up
for Long Term Health Effects
ACS enrolled 1.2M adults in 1982 and a questionnaire assessed age,
sex, race, weight, smoking, education, diet, alcohol, and occupation.
500K adults were linked with air pollution data for metropolitan areas
throughout the U.S. with vital status and cause of death data through
December 31, 1998.
PM 2 5 and S0 2 were associated with all-cause, cardiopulmonary, and
lung cancer mortality.
Each 10jLig/m 3 elevation in PM 2 5 was associated with approximately
4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and
lung cancer mortality, respectively.
Coarse fraction PM 10 _ 2 5 not consistently associated with mortality.
JAMA 2005; 287: 1132-41.
Adjusted Mortality Relative Risk (RR)
Evaluated at Subject-Weighted Mean
Concentrations
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Representative Images of Carbon in Airway
Macrophages from Healthy Children
Carbon in Airway Macrophages and
Lung Function in Children
Alveolar Macrophages (AMs) reflect a particle burden from
occupational/environmental exposure.
Children aged 8-15 U.K. (excluding parental smoking, house with coal
combustion) 64 healthy children, 9 with asthma enrolled. Salivary
cotinine measured.
PM 10 recorded including hourly near traffic plus annual; PFT; induced
sputum with C area calculated under light microscopy.
Each increase in 1.0 jum 2 in C associated with 17% decrease in FEV 1
% predicted and 12.9% in FVC % predicted; Each increase in 1.0
jixg/m 3 PM 10 was associated with a 0.115 urn 2 in C.
Increased primary PM 10 was inversely associated with FEV %
predicted.
NEJM 2006; 355: 21-30.
Associations between Carbon in Airway Macrophages
and Lung Function in Healthy Children
0J5 Q50 0.75 1.00
Median Carbon Area ^m 1 )
Q25 0.50 0.75 1.00
Median Carbon Area (^m 1 )
Field Cancerization of Squamous Cell Carcinoma of the Lung
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Cancer Res 2003; 63: 1727.
SOMAmers: Unique DNA Reagents for Protein Detection
Red, green, purple atoms are modified
nucleotides that provide binding energy
SOMAmer
Target Protein
IN SOLUTION
BOUND COMPLEX
• Single-stranded nucleic acids that bind with high affinity and specificity-currently
available SOMAmers (1,043).
•The limits of detection average (300 fM) and the overall dynamic range spans 7 logs
using different dilutions with a ~6% coefficient of variation.
'PLoS ONE 2010; 5(12): el5003. (December 2010)
SomaLogic
Naive Bayes
n
c
o
1 -Specificity
Bi (mi:! rkei
UniProt ID
Direction*
Description
Cadhemi-1
P12830
down
cell adhesion, transcription regulation
CD30 Ligand
P32971
up
cytokine
w
Endostatin
P39060
up
inhibition of ansioaenesis
4_ K_
HSP 90a
P07900
up
chaperone
LRIG3
Q6UXM1
down
protein binding, tiimor suppressor
MP-4
P55774
up
monokine
Pleiotrophin
P21246
up
growth factor
PRKCl
P41743
up
serine/threonine protein kinase, oncogene
RGM-C
Q6ZYN8
down
iron metabolism
SCFsR
P10721
down
decoy receptor
sL-Selectin
P14151
down
cell adhesion
YES
P07947
up
tyrosine kinase, oncogene
89% sensitivity and 83% specificity
PLoS One. 2010 Dec 7; 5(12):el5003
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