Ann. occup. Hyg., Vol. 46, Supplement 1, pp. 377–381, 2002
© 2002 British Occupational Hygiene Society
Published by Oxford University Press
DOI: 10.1093/annhyg/mef689
Histo-compartmental Analysis of Retained Fine
Particles in the Lungs of London Residents who
Expired at the Time of the Great Smog of 1952
ANDREW HUNT1*, BRET JUDSON1, COLIN L. BERRY2 and
JERROLD L. ABRAHAM1
1Department
of Pathology, State University of New York, Upstate Medical University, 750 East Adams
Street, Syracuse, NY 13210, USA; 2Department of Morbid Anatomy and Histopathology, Queen Mary
and Westfield College, Royal London Hospital, Whitechapel, London E1 1BB, UK
We used scanning electron microscopy to investigate autopsy tissue samples from 18 individuals who died at the time of the London smog event of 1952. Four lung tissue compartments
were specifically targeted for analysis. The greatest diversity of particle types was found in the
recent exposure compartment (aggregated in mucopurulent airway exudate). Metal-bearing
particles were more common in the recent exposure compartment, while non-metal and Fecontaining particles were more abundant in the longer term retention compartments (lymph
nodes and interstitial macrophages). Irrespective of location, these particles were usually
associated with a matrix of carbon particles (∼100 nm in size). These data suggest that metal
particles were an important part of the London aerosol at the time of the 1952 smog and that
such particles are not necessarily preserved long-term in the lung. This lack of biopersistence
may be a function of metal solubility and may have important toxicological implications.
Keywords: fine particles; lung tissue; metals; SEM; smog
We hypothesized that:
INTRODUCTION
There is a demonstrated connection between
increased mortality and morbidity and exposure to
fine particulate matter (PM). The most direct evidence linking exposure to increased risk is to be
obtained from correlating the composition of the
exposure aerosol with recorded increases in mortality. Absolute increases in human mortality with
current levels of ambient PM are so low that the
collection of contemporary material (personal exposure aerosol or inhaled particles) associated with
deaths known to have resulted from PM inhalation is
not practicable. During the London smog episode of
5–9 December 1952 the PM levels rose to 4.5 mg/m3.
Cardio-pulmonary causes of death were the most
common. The estimated total deaths during the
episode was 4000 in excess of that normally expected
(Beaver, 1953). Recent estimates suggest that 12000
excess deaths occurred from December 1952 to
February 1953 because of persisting effects of the
smog (Bell and Davis, 2001).
1. a record of the smog exposure should be present
in specimens of lung tissue from Londoners who
expired at the time of the 1952 smog;
2. clues to the adverse health outcomes in the population could be obtained from an analysis of PM
in such lung tissue;
3. examination of the PM in lung compartments
that represent different residence times in the
lung would provide data on the fate of the
London aerosol PM after inhalation.
MATERIALS AND METHODS
Cases
An increase in autopsies listing chronic obstructive
pulmonary disease (COPD) among major diagnoses
occurred during and after the 1952 smog event.
Cases were retrieved from the autopsy archives of the
Royal London Hospital. Specimens were prepared
by standard pathology laboratory methods for light
microscopy (LM) and scanning electron microscopy
(SEM). Here we present micro-analytical data from
*Author to whom correspondence should be addressed.
e-mail: [email protected]
377
378
A. Hunt et al.
lung tissue from 16 of 18 subjects who died at the
time of the smog (inadequate data was obtained from
the two neonate cases). Details of date of death, cause
of death and subject demographics are presented in
Table 1.
Electron microscopy and microanalysis
Retained PM in lung tissue sections was imaged
for morphology in the secondary electron (SE) mode
of the SEM and imaged for composition in the
backscattered electron (BE) mode. The element
composition of individual inorganic particles was
obtained by energy dispersive X-ray analysis (EDX).
Compartment analysis
Retained PM was analyzed in specific lung
compartments. We hypothesized that PM in each
compartment would reflect the history of residence in
that compartment, with residence time increasing
along the path airways < airspace macrophages <
interstitium < lymph node.
RESULTS
Particle classification
For the sake of brevity individual non-carbonaceous particles were assigned to specific classes
based on consistencies in their composition. In the
case of the metal particles, those classified as Pb type
contained Pb, ± Ca, and/or P, Sn type contained
predominantly Sn without Pb or Zn, Zn type were
almost exclusively Zn, SnZn type consisted of SnZn,
Sb type contained Sb, SbPb types consisted of SbPb,
other metal particle types contained Cu, Ni, Cd and
Mn. Particles containing the element Fe or Ti may
similarly have been a product of anthropogenic
metal-generating processes or they may have been
derived from crustal sources (e.g. windblown soil).
Presented with this uncertainty, we operationally
assigned them to the non-metal category. The nonmetal particle types were classified as Fe type if
composed exclusively of Fe, Fe+ type if Fe was the
dominant element, Ti type if Ti was present, Si type
if composed exclusively of Si, SiAl type if composed of SiAl, SiAl+ type if SiAl were the dominant
elements or other types if the particles contained Ba,
Ca or Al.
Free PM in airway aggregates: compartment 1
Aggregates of inhaled particles were identified in
airways in two cases (cases 1 and 2). These aggregates took the form of black sooty masses associated
with mucopurulent exudate (Fig. 1a,b). The aggregates ranged from ∼0.004 to 0.009 mm2 in crosssection. SE imaging confirmed that these aggregates
consisted of very fine (<1 µm) PM enmeshed in
mucus. Using BE imaging, each aggregate was found
to contain significant amounts of inorganic particles
in a low density (carbonaceous) matrix. High resolution field emission SE imaging confirmed that
each aggregate was composed of ultrafine particles
(<100 nm in size) most of which resembled chain
aggregates of carbon particles (Fig. 1c). EDX analysis identified between 100 and 850 non-carbonaceous
Table 1. Investigated London smog deaths by demographics and major autopsy diagnoses
Case
Age
Sex
Diagnosis 1
Diagnosis 2
1
7 Dec
76
f
Heart failure
Bronchitis
2
23 Jan
61
m
Bronchitisa
Emphysema
3
3 Dec
65
m
Pulmonary embolism
Lung cancer
4
6 Dec
53
m
Heart failure
Bronchitis
5
10 Dec
20 h
m
Prematurity
6
12 Dec
54
f
Emphysema
7
17 Dec
51
f
Sarcoidosis
8
19 Dec
53
m
Heart failure
Bronchitis
9
25 Dec
51
m
Pneumoniaa
TB meningitis
10
4 Jan
60
m
Heart failure
Syphilitic aortitis
11
6 Jan
62
f
Heart failure
Emphysema
12
12 Jan
f
Pneumonia
C.F.?
13
14 Jan
55
m
Bronchitisa
Gastric ulcer
14
17 Jan
64
f
Esophageal cancer
Aspiration
15
23 Jan
44
f
Bronchitisa
Pneumonia
16
28 Jan
62
f
Lung abscessa
17
12 Feb
61
m
Heart failure
Bronchitis
18
5 Mar
66
m
Emphysemaa
MI
aAutopsy
Date of death
6 months
note: condition worsened during smog.
Hodgkins disease
Lungs of Londoners who died in the Great Smog
379
Fig. 1. Case 1. Light micrograph (H&E stain) showing airway exudate containing aggegate of opaque PM (a) and SEM micrograph
of a section of the same aggregate (b), field emission SEM micrograph showing fine PM structure (c), light micrograph (H&E stain)
showing airspace macrophages with abundant PM (d) and light micrograph (H&E stain) showing interstitial particle-laden
macrophages (e).
380
A. Hunt et al.
particles per section. Most of the inorganic particles
were metal-bearing, comprising 51 and 59% of the
total. All metal particle classes were present at >1%
in both cases. The remaining particles were
composed of Si, either alone or in combination with
Al, Mg or Fe (Table 2). These particles ranged from
0.1 (practical limit of detection) to 3.5 µm (median
diameter 0.3 µm).
Airspace macrophages: compartment 2
Particle-laden macrophages were readily observed
in small airways and alveoli (Fig. 1d) in tissue
sections from five cases. The predominant particle
type in the macrophages was finely divided carbonaceous material. BE imaging identified significant
quantities of inorganic particles in these macrophages. Metal-bearing particles constituted between
11 and 25% of the inorganic particles. All metal
classes were present (at >1%) in all cases, with the
exception of Pb (in two cases), Sn (four cases), SnZn
(absent) and Sb (three cases). A variety of non-metal
particles were also recorded (principally Si, either
singly or in association with Al, Mg or Fe).
Interstitial macrophages: compartment 3
Interstitial macrophages with particle loadings
(Fig. 1e) were observed in abundance in 15 cases.
The metal-bearing particle types observed in compartments 1 and 2 were also recorded in the interstitial
macrophages, but in lesser quantities. Of the metal
particle types, Pb and SnZn were absent in all cases.
Sb was present in seven cases, Zn in 10 cases, other
metals in 10 cases, SbPb in 11 cases and Sn in all
cases. In contrast, non-metal particles were found to
be enriched in the interstitial compartments (Table 2).
Lymph node: compartment 4
Macrophages in lymph nodes were identified in
available tissue from two cases. The lymph nodes
were found to be heavily loaded with macrophages
containing fine particles, a proportion of which were
identified as inorganic. Metal particle concentrations
were comparatively less than in the other compartments. Metals comprised 5 and 35% of the noncarbonaceous particles and only the Sn, Sb and SbPb
types were present at >1% in at least one case. The
non-metal particle content was comparably higher
(Table 2).
DISCUSSION
Our examination of lung tissue samples from
London residents who expired at the time of the smog
revealed the presence of a variety of fine PM types
contained in various lung compartments. The most
abundant particle type was ultrafine carbonaceous
material. This combustion product was present in
each compartment. As a group, the next most abundant particle type across all compartments was the
non-metal inorganic particles. Viewed across all
compartments, the metal-bearing particles were least
common. However, the relative abundance of these
two latter particle groups varied depending on the
compartment investigated.
We contend that PM in the form of aggregates free
or exudate-bound in airways represents the most
Table 2. Percentage of retained PM in different lung compartments of two individuals who expired at the time of the 1952 London
smog
Particle type
Percentage of particles in specified lung compartments
Airspace aggregate
Airspace
macrophage
Interstitial macrophages
Lymph node
macrophage
Case 1 (n = 702a) Case 2 (n = 1701) Case 1 (n = 400) Case 1 (n = 857) Case 2 (n = 687) Case 2 (n =1024)
Pb
20
29
1
<1
<1
<1
Sn
17
3
13
10
16
21
Zn
2
2
3
1
0
0
SnZn
9
23
0
0
0
0
Sb
2
1
1
1
9
7
SbPb
2
1
4
2
6
7
Other metal
2
1
3
1
<1
<1
Fe
12
6
20
21
33
24
Fe+
5
5
2
15
2
1
Ti containing
2
2
4
9
12
8
15
16
24
15
6
17
SiAl
3
4
12
9
6
5
SiAl+
1
4
10
13
6
4
Other types
6
4
3
2
4
3
Si
a Number
of particles analyzed in each compartment.
Lungs of Londoners who died in the Great Smog
recent exposure. We consider such PM as having
been retained contemporaneously with the 1952
smog exposure. The PM content of the other
compartments we consider to be representative of
progressively earlier exposures. We would further
argue that during the smog event Londoners were not
exposed to some new PM source.
Rather, we suggest that there was an increased dose
of the typical exposure aerosol, in which case any
difference in the PM content of the various compartments is related to the duration of retention in the
lung. While the carbonaceous PM was a feature of
each analysis compartment, other inorganic PM
components were not constant. There are obvious
differences in PM content between compartments.
Most notably, certain metal-bearing particle types
that are abundant in the most recent retention
compartment (e.g. Pb, Zn and SnZn in the airway
aggregates) are almost totally absent from the longer
term storage compartments. We suggest that such
changes in PM content are a response to variations
in metal solubility. If solubility impacts on physiological processes it may be a factor in PM-mediated
mortality and morbidity.
Recent studies have shown that lung inflammation
is mediated by water-soluble components of common
atmospheric constituents like residual oil fly ash
(Dreher et al., 1997). Moreover, the lung response
has been found to vary with the metal content of the
exposure PM (Kodavanti et al., 1998).
Interestingly, soluble Zn [a metallic element which
we find not to be a retained PM constituent beyond
compartment 1 (airway aggregates)] has been identified (rather than any other metal component) as the
cause of cell injury in animal exposure studies
(Adamson et al., 2000). Zn has also been implicated
381
as the causative agent of impaired respiratory function in mice exposed to combustion products derived
from the burning of coal and municipal sewage
sludge (Fernandez et al., 2001). As Pb has been
greatly reduced or eliminated as a fuel additive, little
current toxicological research related to PM has
focused on the role of Pb. It may be that Pb deserves
more study, as recent analysis of aerosols in Boston
(Godleski et al., 2002) indicates a strong correlation
between Pb and adverse health effects in their animal
studies.
Acknowledgements—This work was supported by the American
Lung Association and the Department of Pathology at SUNY
Upstate Medical University.
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